Rig-I负调控AKT通路参与ATRA和IFNα合用诱导U937细胞增殖抑制、分化、凋亡和周期阻滞
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摘要
正常的造血过程有赖于各种调控因素之间的平衡,正调控因素过多或负调控因素过少,均会造成造血失控。如果造血细胞或其子代细胞进行恶性性增生,即成为血液系统的恶性肿瘤。70年代中期,主要使用抑制恶性细胞增殖的化疗药物对白血病进行治疗,然而,白血病细胞除了恶性增殖外还具有例如分化受阻,凋亡失调和转移的生物学特征。在急性早幼粒细胞性白血病(acute promyelocytic leukemia,APL)病人骨髓中非正常早幼粒细胞积聚的特征明显的表明粒细胞分化受阻。自从1986年我国学者首先使用全反式维甲酸(all-trans retinoic acid,ATRA)分化治疗APL以来,ATRA已成为抗肿瘤药物并且功能上作为一种分化物在APL的治疗中表现出了很好的效果,ATRA的抗增殖活性主要来自于对增长抑制以及诱导分化,此外,在不同的细胞系中ATRA除具有抑制增殖作用外还能促进细胞的凋亡。
维甲酸诱导基因-I(Retinoic acid-inducible gene-I, Rig-I)是含DExD/H box的RNA解旋酶,由925个氨基酸组成,N端包含2个CARD结构域(caspase recruitment domains),C端有1个RNA解旋酶结构域。Rig-I在先天性免疫中发挥重要作用,它可以识别细胞内的病毒RNA,并通过活化IRF3和NF-κB诱导I型干扰素(Type I interferons, IFNs)的产生,目前已成为免疫学领域的研究热点。然而Rig-I最早是在无病毒感染下ATRA诱导APL细胞株NB4分化时分离到的一个受调表达的基因,其与ATRA诱导的粒系分化通路密切相关。与其在抗病毒天然免疫方面的研究相比,到目前为止,Rig-I在造血细胞中的结构与功能以及信号传导方面的研究仍然不是很清楚。特别是与APL细胞系NB4(AML-M3型)同为急性髓系白血病(acute myeloid leukemia, AML)细胞系的人急性单核白血病细胞系U937(AML-M5型)在ATRA和干扰素(interferon, IFN)作用下Rig-I的功能及信号通路的研究未见报道。
本实验首先在制备了小鼠Rig-I和人的Rig-I-N抗体并分别建立了诱导表达人Rig-I和调控Rig-I沉默的U937细胞基础上,研究ATRA和IFN对U937细胞增殖、分化、凋亡和周期影响并在此过程中对Rig-I的功能和信号通路进行了研究。
主要得出以下结论:
1.分别将小鼠Rig-I全长基因和人Rig-I-N 850bp序列构建到了原核表达载体,在大肠杆菌中得到了表达,纯化了小鼠Rig-I和人Rig-I-N的融合蛋白,并以此为抗原分别制备了特异性良好的多克隆抗体,制备的抗体能够识别在原核和真核表达系统中表达的各自抗原蛋白,并结合小鼠脾脏细胞Western blot分析和U937细胞免疫荧光技术表明制备的小鼠Rig-I和人Rig-I-N多克隆抗体具有良好的免疫特异性。
2.通过PCR技术将人Rig-I基因构建到Tet-Off诱导表达系统的反应质粒pTRE2 -hyg中,转入293(Tet-Off)细胞验证Rig-I的表达后电转入U937(Tet-Off)细胞,筛选混合克隆细胞,对其单克隆化,Western blot挑选出撤Tetracycline后能够很好的诱导表达Rig-I的单克隆并结合细胞免疫荧光技术验证Rig-I的表达,得到了利用Tet-Off诱导表达系统表达Rig-I的U937细胞。
3.将设计好的两条人Rig-I基因shRNA miR-30结构不完全序列PCR扩增为完全miR-30结构序列后构建到慢病毒表达载体p201中,在293T细胞中表明其具有很明显的RNAi效果,将其构建到Tet-Off系统中带有GFP的反应质粒pTRE-GFP-hyg后转入U937(Tet-Off)细胞,筛选出稳定混合克隆细胞并对其单克隆化,利用报告基因GFP表达及Western blot方法挑选RNAi作用明显的单克隆细胞并验证其RNAi的调控性,建立了基于Tet-Off系统调控的稳定Rig-I基因RNAi的U937细胞。
4.ATRA、IFNα、IFNγ单独使用对U937细胞的增殖起到抑制作用,组合使用,特别是ATRA和IFNα合用显著的抑制其增殖,细胞周期分析也表现出相同的结果,绝大部分阻滞在G0/G1期;ATRA单独使用对细胞分化作用明显,ATRA和IFNα合用对分化和凋亡有协同作用。因此,ATRA和IFNα合用对于U937增殖抑制、分化、凋亡和周期阻滞具有协同增效的作用。
5.U937单用ATRA和IFNγ对Rig-I诱导表达不明显,而单用IFNα对Rig-I诱导显著,尤其是ATRA和IFNα合用对Rig-I的诱导表达具有协同作用。与在ATRA和IFNα合用下诱导Rig-I基因上调表达的U937细胞相比,在相同条件下Rig-I沉默的U937细胞呈现相反的结果,表现为增殖明显、分化、凋亡减少,周期阻滞部分解除。正反两方面研究结果说明Rig-I的表达上调参与了ATRA和IFNα合用诱导U937细胞增殖抑制、分化、凋亡和周期阻滞。
6.对细胞信号通路的研究表明ATRA和IFNα合用诱导Rig-I表达能够抑制AKT和AKT-mTOR通路下游P70和4EBP1的磷酸化活化,并抑制AKT下游另一靶蛋白FOXO3α转录因子磷酸化,促进P27周期阻滞蛋白的表达,而在相同条件下Rig-I沉默的U937细胞促进AKT及其通路的活化,而AKT及AKT信号通路对肿瘤细胞的增殖、分化、凋亡和周期起着决定性的作用,因此,Rig-I负调控AKT通路参与ATRA和IFNα诱导的U937细胞增殖抑制、分化、凋亡和周期阻滞。
The normal regulation of hematopoiesis depends on the balance among various factors, regulatory factors are too many or negative regulatory factors are too few will cause out of control of hematopoiesis. If the hematopoietic cells or their progeny cells are malignant hyperplasia, it becomes the malignancy of blood system. Mid-70s, mainly using chemotherapeutic drugs of inhibiting the proliferation of malignant cells to treat the leukemia, In addition to malignant proliferation, leukemic cells have the biologic characteristics of blocked differentiation, apoptosis disorders and metastasis. In APL (acute promyelocytic leukemia) patients, unnatural accumulation of promyelocytic cells in bone marrow show the characteristics of granule cells significantly blocked. Since 1986, Chinese scholars firstly using ATRA (all-trans retinoic acid) to treat APL, ATRA has become an antitumor drug and as a material of differentiation therapy has demonstrated very good results in the treatment of APL. anti-proliferation activity of ATRA mainly comes from the growth inhibition and induction of differentiation, moreover, in addition to inhibit the proliferation, ATRA also promotes apoptosis in different cell lines.
Rig-I (Retinoic acid-inducible gene-I) is a RNA helicase with DExD / H box, composed with the 925 amino acid residues, N terminal contains 2 CARD domain (caspase recruitment domains), C terminal has an RNA helicase domain. Rig-I plays an important role in innate immunity, it can identify the virus RNA within the cell, and induce the production of IFNs (typeⅠinterferon through the activation of IRF3 and NF-kB, now has become a hot topic in immunology. However Rig-I was firstly isolated from NB4 of APL cell line which is induced differentiation with ATRA in the absence of virus infection, and is closely related with the ATRA-induced granulocytic differentiation pathways. Compared with the research of anti-virus in innate immunity. So far, it is still not clear of the structure and function, signal transduction of Rig-I in hematopoietic cell. Especially, It has not report about the function and signaling pathway of Rig-I in U937 (human acute monocytic leukemia cell line; AML-M5) belonging to AML (acute myeloid leukemia) with NB4 (APL cell line; AML-M3) under the action of ATRA and IFN (interferon).
In this study, first of all, on the basis of preparation of the mouse and human Rig-I antibody, establishing the induced expression of human Rig-I and regulatory Rig-I RNAi U937 cell lines separately, studied the effect of cell proliferation, differentiation, apoptosis and cell cycle on U937 under the action of ATRA and IFN, in the process of above, Rig-I function and signaling pathways have been studied.
The main results were as follows:
1. The mRig-I (full-length gene of Rig-I in mouse) and hRig-I-N (850 bp sequence of human Rig-I N terminal) were built into the prokaryotic expression vector, expressed in E. coli, fusion proteins of mRig-I and hRig-I-N were purified and separately prepared for the polyclonal antibodies of good specificity, the prepared antibodies can identify the expression of respective antigens from prokaryotic and eukaryotic expression system and Combined with mouse spleen cells and immunofluorescence technique of U937 cells indicate that polyclonal antibodies of mRig-I and hRig-I-N have a good immune specificity.
2. By PCR, hRig-I gene was constructed into the pTRE2-hyg response plasmid of the Tet-Off inducible expression system, after transformed into 293 (Tet-Off) cells and verified the expression of Rig-I, the constructed plasmid was electroporated into the U937 (Tet-Off) cells, cells were selected and isolated, after withdrawal of Tetracycline, clones which can be well induced expression of Rig-I were picked by Western and combined with immunofluorescence verified Rig-I expression, the U937 can be induced expression of Rig-I was obtained by using Tet-Off inducible expression system.
3. Two designed shRNA miR-30 partial sequences of human Rig-I were amplify to complete sequences of miR-30 structure and constructed into the p201 lentiviral vector, after indicated have obvious RNAi effect in 293T, the two complete shRNA sequences were built into response plasmid of pTRE2-GFP-hyg and electroporated into the U937 (Tet-Off) cells, these cells were selected and isolated, clones were picked and verified the RNAi regulation by using the expression of GFP report gene and Western blot technique, the regulatable Rig-I RNAi stable U937 was established based on the Tet-Off system.
4. ATRA, IFNα, IFNγalone inhibited the U937 cell proliferation, in combination, in particular, ATRA and IFNαcombination significantly inhibited the cell proliferation, cell cycle analysis also showed the same result, most blocked in the G0/G1 period; ATRA alone has obvious effect on cell differentiation, ATRA and IFNαcombination have the synergy effect on differentiation and apoptosis. Therefore, ATRA and IFNαcombination show a synergistic effect on the proliferation inhibition, differentiation, apoptosis and cell cycle arrest of U937.
5. The Rig-I expression of U937 induced by ATRA or IFNγalone is not obvious, but the induction of the Rig-I is significantly by IFNαalone, especially it was show a synergistic effect on the induced expression of Rig-I by ATRA and IFNαcombination. Compared with the upregulated expression of Rig-I in U937 combination ATRA with IFNα, under the same conditions, Rig-I silent U937 cells showed the opposite results, showing significant proliferation, differentiation and apoptosis reduction, cycle arrest partially relieved. Both positive and negative Research showed that upregulated expression of Rig-I involved in proliferation inhibition, differentiation, apoptosis and cell cycle arrest of U937 cells induced by ATRA and IFNαcombination.
6. Research on the cell signaling pathway of U937 showed that Rig-I expression induced by the combination of ATRA and IFNαcan inhibit the phosphorylation and activation of not only AKT but also P70 and 4EBP1 which is the downstream of AKT-mTOR pathway, also inhibit the phosphorylation of transcription factor FOXO3α, another AKT downstream target protein, to promote P27 cycle arrest protein expression, Under the same conditions the silence of Rig-I can promote activation of AKT and its downstream pathway, The AKT and AKT signaling pathway play a decisive role on proliferation, differentiation, apoptosis and cell cycle of tumor cell, therefore, through negative regulation of AKT pathway Rig-I involved in ATRA and IFNαinduced cell proliferation inhibition, differentiation, apoptosis cell cycle arrest of U937.
维甲酸诱导基因-I(Retinoic acid-inducible gene-I, Rig-I)是含DExD/H box的RNA解旋酶,由925个氨基酸组成,N端包含2个CARD结构域(caspase recruitment domains),C端有1个RNA解旋酶结构域。Rig-I在先天性免疫中发挥重要作用,它可以识别细胞内的病毒RNA,并通过活化IRF3和NF-κB诱导I型干扰素(Type I interferons, IFNs)的产生,目前已成为免疫学领域的研究热点。然而Rig-I最早是在无病毒感染下ATRA诱导APL细胞株NB4分化时分离到的一个受调表达的基因,其与ATRA诱导的粒系分化通路密切相关。与其在抗病毒天然免疫方面的研究相比,到目前为止,Rig-I在造血细胞中的结构与功能以及信号传导方面的研究仍然不是很清楚。特别是与APL细胞系NB4(AML-M3型)同为急性髓系白血病(acute myeloid leukemia, AML)细胞系的人急性单核白血病细胞系U937(AML-M5型)在ATRA和干扰素(interferon, IFN)作用下Rig-I的功能及信号通路的研究未见报道。
本实验首先在制备了小鼠Rig-I和人的Rig-I-N抗体并分别建立了诱导表达人Rig-I和调控Rig-I沉默的U937细胞基础上,研究ATRA和IFN对U937细胞增殖、分化、凋亡和周期影响并在此过程中对Rig-I的功能和信号通路进行了研究。
主要得出以下结论:
1.分别将小鼠Rig-I全长基因和人Rig-I-N 850bp序列构建到了原核表达载体,在大肠杆菌中得到了表达,纯化了小鼠Rig-I和人Rig-I-N的融合蛋白,并以此为抗原分别制备了特异性良好的多克隆抗体,制备的抗体能够识别在原核和真核表达系统中表达的各自抗原蛋白,并结合小鼠脾脏细胞Western blot分析和U937细胞免疫荧光技术表明制备的小鼠Rig-I和人Rig-I-N多克隆抗体具有良好的免疫特异性。
2.通过PCR技术将人Rig-I基因构建到Tet-Off诱导表达系统的反应质粒pTRE2 -hyg中,转入293(Tet-Off)细胞验证Rig-I的表达后电转入U937(Tet-Off)细胞,筛选混合克隆细胞,对其单克隆化,Western blot挑选出撤Tetracycline后能够很好的诱导表达Rig-I的单克隆并结合细胞免疫荧光技术验证Rig-I的表达,得到了利用Tet-Off诱导表达系统表达Rig-I的U937细胞。
3.将设计好的两条人Rig-I基因shRNA miR-30结构不完全序列PCR扩增为完全miR-30结构序列后构建到慢病毒表达载体p201中,在293T细胞中表明其具有很明显的RNAi效果,将其构建到Tet-Off系统中带有GFP的反应质粒pTRE-GFP-hyg后转入U937(Tet-Off)细胞,筛选出稳定混合克隆细胞并对其单克隆化,利用报告基因GFP表达及Western blot方法挑选RNAi作用明显的单克隆细胞并验证其RNAi的调控性,建立了基于Tet-Off系统调控的稳定Rig-I基因RNAi的U937细胞。
4.ATRA、IFNα、IFNγ单独使用对U937细胞的增殖起到抑制作用,组合使用,特别是ATRA和IFNα合用显著的抑制其增殖,细胞周期分析也表现出相同的结果,绝大部分阻滞在G0/G1期;ATRA单独使用对细胞分化作用明显,ATRA和IFNα合用对分化和凋亡有协同作用。因此,ATRA和IFNα合用对于U937增殖抑制、分化、凋亡和周期阻滞具有协同增效的作用。
5.U937单用ATRA和IFNγ对Rig-I诱导表达不明显,而单用IFNα对Rig-I诱导显著,尤其是ATRA和IFNα合用对Rig-I的诱导表达具有协同作用。与在ATRA和IFNα合用下诱导Rig-I基因上调表达的U937细胞相比,在相同条件下Rig-I沉默的U937细胞呈现相反的结果,表现为增殖明显、分化、凋亡减少,周期阻滞部分解除。正反两方面研究结果说明Rig-I的表达上调参与了ATRA和IFNα合用诱导U937细胞增殖抑制、分化、凋亡和周期阻滞。
6.对细胞信号通路的研究表明ATRA和IFNα合用诱导Rig-I表达能够抑制AKT和AKT-mTOR通路下游P70和4EBP1的磷酸化活化,并抑制AKT下游另一靶蛋白FOXO3α转录因子磷酸化,促进P27周期阻滞蛋白的表达,而在相同条件下Rig-I沉默的U937细胞促进AKT及其通路的活化,而AKT及AKT信号通路对肿瘤细胞的增殖、分化、凋亡和周期起着决定性的作用,因此,Rig-I负调控AKT通路参与ATRA和IFNα诱导的U937细胞增殖抑制、分化、凋亡和周期阻滞。
The normal regulation of hematopoiesis depends on the balance among various factors, regulatory factors are too many or negative regulatory factors are too few will cause out of control of hematopoiesis. If the hematopoietic cells or their progeny cells are malignant hyperplasia, it becomes the malignancy of blood system. Mid-70s, mainly using chemotherapeutic drugs of inhibiting the proliferation of malignant cells to treat the leukemia, In addition to malignant proliferation, leukemic cells have the biologic characteristics of blocked differentiation, apoptosis disorders and metastasis. In APL (acute promyelocytic leukemia) patients, unnatural accumulation of promyelocytic cells in bone marrow show the characteristics of granule cells significantly blocked. Since 1986, Chinese scholars firstly using ATRA (all-trans retinoic acid) to treat APL, ATRA has become an antitumor drug and as a material of differentiation therapy has demonstrated very good results in the treatment of APL. anti-proliferation activity of ATRA mainly comes from the growth inhibition and induction of differentiation, moreover, in addition to inhibit the proliferation, ATRA also promotes apoptosis in different cell lines.
Rig-I (Retinoic acid-inducible gene-I) is a RNA helicase with DExD / H box, composed with the 925 amino acid residues, N terminal contains 2 CARD domain (caspase recruitment domains), C terminal has an RNA helicase domain. Rig-I plays an important role in innate immunity, it can identify the virus RNA within the cell, and induce the production of IFNs (typeⅠinterferon through the activation of IRF3 and NF-kB, now has become a hot topic in immunology. However Rig-I was firstly isolated from NB4 of APL cell line which is induced differentiation with ATRA in the absence of virus infection, and is closely related with the ATRA-induced granulocytic differentiation pathways. Compared with the research of anti-virus in innate immunity. So far, it is still not clear of the structure and function, signal transduction of Rig-I in hematopoietic cell. Especially, It has not report about the function and signaling pathway of Rig-I in U937 (human acute monocytic leukemia cell line; AML-M5) belonging to AML (acute myeloid leukemia) with NB4 (APL cell line; AML-M3) under the action of ATRA and IFN (interferon).
In this study, first of all, on the basis of preparation of the mouse and human Rig-I antibody, establishing the induced expression of human Rig-I and regulatory Rig-I RNAi U937 cell lines separately, studied the effect of cell proliferation, differentiation, apoptosis and cell cycle on U937 under the action of ATRA and IFN, in the process of above, Rig-I function and signaling pathways have been studied.
The main results were as follows:
1. The mRig-I (full-length gene of Rig-I in mouse) and hRig-I-N (850 bp sequence of human Rig-I N terminal) were built into the prokaryotic expression vector, expressed in E. coli, fusion proteins of mRig-I and hRig-I-N were purified and separately prepared for the polyclonal antibodies of good specificity, the prepared antibodies can identify the expression of respective antigens from prokaryotic and eukaryotic expression system and Combined with mouse spleen cells and immunofluorescence technique of U937 cells indicate that polyclonal antibodies of mRig-I and hRig-I-N have a good immune specificity.
2. By PCR, hRig-I gene was constructed into the pTRE2-hyg response plasmid of the Tet-Off inducible expression system, after transformed into 293 (Tet-Off) cells and verified the expression of Rig-I, the constructed plasmid was electroporated into the U937 (Tet-Off) cells, cells were selected and isolated, after withdrawal of Tetracycline, clones which can be well induced expression of Rig-I were picked by Western and combined with immunofluorescence verified Rig-I expression, the U937 can be induced expression of Rig-I was obtained by using Tet-Off inducible expression system.
3. Two designed shRNA miR-30 partial sequences of human Rig-I were amplify to complete sequences of miR-30 structure and constructed into the p201 lentiviral vector, after indicated have obvious RNAi effect in 293T, the two complete shRNA sequences were built into response plasmid of pTRE2-GFP-hyg and electroporated into the U937 (Tet-Off) cells, these cells were selected and isolated, clones were picked and verified the RNAi regulation by using the expression of GFP report gene and Western blot technique, the regulatable Rig-I RNAi stable U937 was established based on the Tet-Off system.
4. ATRA, IFNα, IFNγalone inhibited the U937 cell proliferation, in combination, in particular, ATRA and IFNαcombination significantly inhibited the cell proliferation, cell cycle analysis also showed the same result, most blocked in the G0/G1 period; ATRA alone has obvious effect on cell differentiation, ATRA and IFNαcombination have the synergy effect on differentiation and apoptosis. Therefore, ATRA and IFNαcombination show a synergistic effect on the proliferation inhibition, differentiation, apoptosis and cell cycle arrest of U937.
5. The Rig-I expression of U937 induced by ATRA or IFNγalone is not obvious, but the induction of the Rig-I is significantly by IFNαalone, especially it was show a synergistic effect on the induced expression of Rig-I by ATRA and IFNαcombination. Compared with the upregulated expression of Rig-I in U937 combination ATRA with IFNα, under the same conditions, Rig-I silent U937 cells showed the opposite results, showing significant proliferation, differentiation and apoptosis reduction, cycle arrest partially relieved. Both positive and negative Research showed that upregulated expression of Rig-I involved in proliferation inhibition, differentiation, apoptosis and cell cycle arrest of U937 cells induced by ATRA and IFNαcombination.
6. Research on the cell signaling pathway of U937 showed that Rig-I expression induced by the combination of ATRA and IFNαcan inhibit the phosphorylation and activation of not only AKT but also P70 and 4EBP1 which is the downstream of AKT-mTOR pathway, also inhibit the phosphorylation of transcription factor FOXO3α, another AKT downstream target protein, to promote P27 cycle arrest protein expression, Under the same conditions the silence of Rig-I can promote activation of AKT and its downstream pathway, The AKT and AKT signaling pathway play a decisive role on proliferation, differentiation, apoptosis and cell cycle of tumor cell, therefore, through negative regulation of AKT pathway Rig-I involved in ATRA and IFNαinduced cell proliferation inhibition, differentiation, apoptosis cell cycle arrest of U937.
引文
沈树红. 2005.维甲酸诱导基因-I对髓系造血的调控及分子机制研究. [博士学位论文].上海:上海第二医科大学
孙逸武. 1997.早幼粒细胞白血病诱导分化过程中维甲酸调控基因的研究. [博士学位论文].上海:上海第二医科大学
张囡囡. 2009.维甲酸诱导基因-I(Rig-I)对正常和白血病髓系造血的调控作用和相关分子机制研究. [博士学位论文].上海:中科院上海健康研究所
Actor B, Cobbers J M, Buschges R, Wolter M, Knobbe C B, Lichter P, Reifenberger G, Weber R G. 2002. Comprehensive analysis of genomic alterations in gliosarcoma and its two tissue components. Genes Chromosomes Cancer, 34: 416~427
Akira S, Uematsu S, Takeuchi O. 2006. Pathogen recognition and innate immunity. Cell, 124: 783~801
Alessi D R, Kozlowski M T, Weng Q P, Morrice N, Avruch J. 1998. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro. Curr Biol, 8: 69~81
Alff P J, Sen N, Gorbunova E, Gavrilovskaya I N, Mackow E R. 2008. The NY-1 hantavirus Gn cytoplasm ic tail coprecipitates TRAF3 and inhibits cellular interferon responses by disrupting TBK1–TRAF3 complex formation. J Virol, 82(18): 9115~9122
Ameres S L, Martinez J, Schroeder R. 2007. Molecular basis for target RNA recognition and cleavage by human RISC. Cell, 130: 101~112
Andrejeva J, Childs K S, Young D F, Carlos T S, Stock N, Goodbourn S, Randall R E. 2004. The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-b promoter. Proc Natl Acad Sci USA, 101(49): 17264~17269
Andrejeva J, Childs K S, Young D F, Carlos T S, Stock N, Goodbourn S. 2004. The V proteins of paramy xoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc Natl Acad Sci U S A, 101(49): 17264~17269
Aoki M, Blazek E, Vogt PK. 2001. A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt. Proc Natl Acad Sci U S A, 98: 136~141
Aoki M, Jiang H, Vogt P K. 2004. Proteasomal degradation of the FoxO1 transcriptional regulator in cells transformed by the P3k and Akt oncoproteins. Proc Natl Acad Sci USA, 101: 13613~13617
Arbiser J L, Kau T, Konar M, Narra K, Ramchandran R, Summers S A, Vlahos C J, Ye K, Perry B N, Matter W, Fischl A, Cook J, Silver P A, Bain J, Cohen P, Whitmire D, Furness S, Govindarajan B, Bowen J P. 2007. Solenopsin, the alkaloidal component of the fire ant (Solenopsis invicta), is a naturally occurring inhibitor of phosphatidylinositol-3-kinase signaling and angiogenesis. Blood, 109: 560~565
Arimoto K, Takahashi H, Hishiki T, Konishi H, Fujita T, Shimotohno K. 2007. Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proc Natl Acad Sci USA, 104: 7500~5
Avdulov S, Li S, Michalek V, Burrichter D, Peterson M, Perlman D M, Manivel J C, Sonenberg N, Yee D, Bitterman P B, Polunovsky V A. 2004. Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells. Cancer Cell, 5: 553~563
Avruch J, Belham C, Weng Q, Hara K, Yonezawa K. 2001. The p70 S6 kinase integrates nutrient and growth signals to control translational capacity. Prog Mol Subcell Biol, 26: 115~154
Bachman K E, Argani P, Samuels Y, Silliman N, Ptak J, Szabo S, Konishi H, Karakas B, Blair B G, Lin C, Peters B A, Velculescu V E, Park B H. 2004. The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther, 3: 772~775
Backers K, Blero D, Paternotte N, Zhang J, Erneux C. 2003. The termination of PI3K signalling by SHIP1 and SHIP2 inositol5-phosphatases. Adv Enzyme Regul, 43: 15~28
Backman S A, Ghazarian D, So K, Sanchez O, Wagner K U, Hennighausen L, Suzuki A, Tsao M S, Chapman W B, Stambolic V, Mak T W. 2004. Early onset of neoplasia in the prostate and skin of mice with tissuespecific deletion of Pten. Proc Natl Acad Sci U S A, 101: 1725~1730
Bakker W J, Blazquez-Domingo M, Kolbus A, Besooyen J, Steinlein P, Beug H, Coffer P J, Lowenberg B, Von Lindern M and Van Dijk TB. 2004. FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1. J Cell Biol, 164: 175~184
Balachandran S, Venkataraman T, Fisher P B, Barber G N. 2007. Fas-associated death domain-containing protein-mediated antiviral innate immune signaling involves the regulation of Irf7. J Immunol, 178(4): 2429~2439
Ballif B A, Roux P P, Gerber S A, MacKeigan J P, Blenis J, Gygi S P. 2005. Quantitative phosphorylation profiling of the ERK/p90 ribosomal S6 kinase-signaling cassette and its targets, the tuberous sclerosis tumor suppressors. Proc Natl Acad Sci USA, 102: 667~672
Bamming D, Horvath C M. 2009. Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I and LGP2. J Biol Chem, 284: 9700~12
Baron U, Freundlieb S, Gossen M, Bujard H. 1995. Co-regulation of two gene activities by tetracycline via a bidirectional promoter. Nucleic Acids Res, 23: 3605~3606
Barral P M, Morrison J M, Drahos J, Gupta P, Sarkar D, Fisher P B, Racaniello V R. 2007. MDA-5 is cleaved in poliovirus-infected cells. J Virol, 81: 3677~3684
Barral P M, Morrison J M, Drahos J, Gupta P, Sarkar D, Fisher P B, Racaniello V R. 2007. MDA-5 is cleaved in poliovirus-infected cells. J Virol, 81(8): 3677~3684
Barro M, Patton J T. 2007. Rotavirus NSP1 inhibits expression of type I interferon by antagonizing the function of interferon regulatory factors IRF3, IRF5, and IRF7. J Virol, 81(9): 4473~4481
Bauer S, Pigisch S, Hangel D, Kaufmann A, Hamm S. 2008. Recognition of nucleic acid and nucleic acid analogs by Toll-like receptors 7, 8 and 9. Immunobiology, 213: 315~28
Bauhofer O, Summerfield A, Sakoda Y, Tratschin J D, Hofmann M A, Ruggli N. 2007. Classical swine fever virus Npro interacts with interferon regulatory factor3 and induces its proteasomal degradation. J Virol, 81(7): 3087~3096
Bellacosa A, de Feo D, Godwin A K, Bell D W, Cheng J Q, Altomare D A, Wan M, Dubeau L, Scambia G, Masciullo V, Ferrandina G, Benedetti P P, Mancuso S, Neri G, Testa J R. 1995. Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int J Cancer 64: 280~285
Bellacosa A, Kumar C C, Di Cristofano A, Testa J R. 2005. Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res, 94:29~86
Benthin M, Dallmann I, Atzpodien J. 2001. 13cis- and all-transretinoic acid have antiproliferative effects on CML cells and render IFN alpha antiproliferative potency after combined treatment in vitro. Cancer Biother Radiopharm, 16: 323~331
Bernard J, Mathe G, Boulay J, Ceoard B, Chome J. 1959. Acute promyelocytic leukemia: a study made on 20 cases. Schweiz Med Wochenschr, 89: 604~608
Bernard J, Weil M, Boiron M. 1973. Acute promyelocytic leukemia: results of treatment by daunorubicin. Blood, 41: 489~496
Biggs W H, Meisenhelder J, Hunter T, Cavenee W K, Arden K C. 1999. Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci USA, 96: 7421~7426
Birck A, Ahrenkiel V, Zeuthen J, Hou-Jensen K, Guldberg P. 2000. Mutation and allelic loss of the PTEN/MMAC1 gene in primary and metastatic melanoma biopsies. J Invest Dermatol, 114: 277~280
Boone D L, Turer E E, Lee E G, Ahmad R C, Wheeler M T, Tsui C, Hurley P, Chien M, Chai S, Hitotsumatsu O, McNally E, Pickart C, Ma A. 2004. The ubiquitin-modifying enzyme A20 is required for termination of toll-like receptor responses. Nat Immunol, 5: 1052~60
Brazil D P, Yang Z Z, Hemmings B A. 2004. Advances in protein kinase B signalling: AKTion on multiple fronts. Trends Biochem Sci, 29: 233~242
Breitman T R, Collins S J, Keene B R. 1981. Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid. Blood, 57: 1000~1004
Breitman T R, Selonick S E, Collins S J. 1980. Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci U S A, 77: 2936~2940
Broderick D K, Di C, Parrett T J, Samuels Y R, Cummins J M, McLendon R E, Fults D W, Velculescu V E, Bigner D D, Yan H. 2004. Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas. Cancer Res, 64: 5048~5050
Brown D, Kogan S, Lagasse E, Brown D, Kogan S, Lagasse E, Weissman I, Alcalay M, Pelicci PG, Atwater S, Bishop JM. 1997. A PMLRARalpha transgene initiates murine acute promyelocytic leukemia. Proc Natl Acad Sci U S A, 94: 2551~2556
Brownawell A M, Kops G J, Macara I G, Burgering B M. 2001. Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular distribution and activity of the forkhead transcription factor AFX. Mol Cell Biol, 21: 3534~3546
Brunet A, Bonni A, Zigmond M J, Lin M Z, Juo P, Hu L S, Anderson M J, Arden K C, Blenis J and Greenberg ME. 1999. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell, 96: 857~868
Brunet A, Kanai F, Stehn J, Xu J, Sarbassova D, Frangioni J V, Dalal S N, DeCaprio J A, Greenberg M E, Yaffe M B. 2002.14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport. J Cell Biol, 156: 817~828
Burckstummer T, Baumann C, Blüml S, Dixit E, Dürnberger G, Jahn H, Planyavsky M, Bilban M, Colinge J, Bennett K L, Superti-Furga G. 2009. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol, 10(3): 266~272
Burgering B M, Coffer P J. 1995. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature, 376: 599~602
Byun D S, Cho K, Ryu B K, Lee M G, Park J I, Chae K S, Kim H J, Chi S G. 2003. Frequent monoallelic deletion of PTEN and its reciprocal association with PIK3CA amplification in gastric carcinoma. Int J Cancer, 104: 318~327
Campbell I G, Russell S E, Choong D Y, Montgomery K G, Ciavarella M L, Hooi C S, Cristiano B E, Pearson R B, Phillips W A. 2004. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res, 64: 7678~7681
Cantley L C, Neel B G. 1999. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A, 96: 4240~4245 Cantley L C. 2002. The phosphoinositide 3-kinase pathway, Science 296:1655~1657
Carmeliet P, Lampugnani M G, Moons L, Breviario F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oostuyse B, Dewerchin M, Zanetti A, Angellilo A, Mattot V, Nuyens D, Lutgens E, Clotman F, de Ruiter M C, Gittenberger-de Groot A, Poelmann R, Lupu F, Herbert J M, Collen D, Dejana E. 1999. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell, 98: 147~157
Cassady K A. 2005. Human cytomegalovirus TRS1 and IRS1 gene products block the double-stranded- RNA-activated host protein shut off response induced by herpes simplex virus type 1 infection. J Virol, 79(14): 8707~8715
Castaigne S, Chomienne C, Daniel M T, Ballerini P, Berger R, Fenaux P, Degos L. 1990. All trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia, I: clinical results. Blood, 76: 1704~1709
Castedo M, Ferri K F, Kroemer G. 2002. Mammalian target of rapamycin (mTOR): pro and anti-apoptotic. Cell Death Differ, 9: 99~100
Chan S, Scheulen M E, Johnston S, Mross K, Cardoso F, Dittrich C, Eiermann W, Hess D, Morant R, Semiglazov V, Borner M, Salzberg M, Ostapenko V, Illiger H J, Behringer D, Bardy-Bouxin N, Boni J, Kong S, Cincotta M, Moore L. 2005. Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol, 23: 5314~5322
Chang K, Elledge S J, Harmon G J. 2006. Lessons from nature: microRNA-based shRNA libraries. Nat Methods, 3(9):707~714
Chen W S, Xu P Z, Gottlob K, Chen M L, Sokol K, Shiyanova T. 2001. Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes Dev,15: 2203~2208
Chen Z X, Xue Y Q, Zhang R, Chen Z X, Xue Y Q, Zhang R, Tao R F, Xia X M, Li C, Wang W, Ling B J. 1991. A clinical and experimental study on all-trans retinoic acid treated acute promyelocytic leukemia patients.Blood, 78: 1413~1419
Chen Z, Brand NJ, Chen A, Chen Z, Brand N J, Chen A, Chen S J, Tong J H, Wang Z Y, Waxman S, Zelent A . 1993. Fusion between a novel Kruppel-like zinc finger gene and the retinoic acidreceptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J, 12: 1161~1167
Cheng G X, Zhu X H, Men X Q. 1999. Distinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF-RARalpha and NPM-RARalpha. Proc Natl Acad Sci U S A, 96: 6318~6323
Cheng J Q, Ruggeri B, Klein W M, Sonoda G, Altomare D A, Watson D K, Testa J R. 1996. Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci U S A, 93: 3636~3641
Child S J, Hakki M, De Niro, K L, Geballe A P. 2004. Evasion of cellular antiviral responses by human cytomegalovirus TRS1 and IRS1. J Virol, 78(1): 197~205
Childs K S, Andrejeva J, Randall R E, Goodbourn S. 2008. Mechanism of mda-5 inhibition by paramyxov irus V proteins. J Virol, 83(3): 1465~1473
Childs K, Stock N, Ross C, Andrejeva J, Hilton L, Skinner M. 2007. mda-5, but not RIG-I, is a common target for paramyxovirus V proteins. Virology, 359(1): 190~200
Chinnaiyan A M., O Rourke K, Tewari M, Dixit V M. 1995. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell, 81(4): 505~512
Choi K M, McMahon L P, Lawrence J C. 2003. Two motifs in the translational repressor PHAS-I required for efficient phosphorylation by mammalian target of rapamycin and for recognition by raptor. J Biol Chem, 278: 19667~19673
Chow S, Minden M D, Hedley DW. 2006. Constitutive phosphorylation of the S6 ribosomal protein via mTOR and ERK signaling in the peripheral blasts of acute leukemia patients. Exp Hematol, 34: 1183~1191
Corey S, Eguinoa A, Puyana-Theall K, Bolen J B, Cantley L, Mollinedo F, Jackson T R, Hawkins P T, Stephens L R. 1993. Granulocyte macrophage-colony stimulating factor stimulates both association and activation of phosphoinositide 3OH-kinase and src-related tyrosine kinase(s) in human myeloid derived cells. EMBO J, 12: 2681~2690
Cui S, Eisenacher K, Kirchhofer A, Brzozka K, Lammens A, Lammens K, Fujita T, Hopfner K P. 2008. The C-terminal regulatory domain is the RNA 5-triphosphate sensor of RIG-I. Mol Cell, 29: 169~79
Cui Y, Li M, Walton K D, Sun K, Hanover J A, Furth P A, Hennighausen L. 2001. The Stat3 ? 5 locus encodesnovel endoplasmic reticulum and helicase like proteins that are preferentially expressed in normal and neoplastic mammary tissue. Genomics, 78: 129~134
Cunningham I, Gee T S, Reich L M, Kempin S J, Naval A N, Clarkson BD. 1989. Acute promyelocytic leukemia: treatment results during a decade at Memorial Hospital. Blood, 73: 1116~1122
Daenen S, Vellenga E, Dobbenburgh O A, Halie M R. 1986. Retinoic acid as antileukemic therapy in a patient with acute promyelocytic leukemia and Aspergillus pneumonia. Blood, 67: 559~561
Datta S R, Dudek H, Tao X, Datta S R, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg M E. 1997. Akt phosphorylation of BAD couples survival signalsto the cell-intrinsic death machinery. Cell, 91: 231~241
de The′H, Chomienne C, Lanotte M, Degos L, Dejean A. 1990. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature, 347: 558~561
Degos L ,Chomienne C, Daniel M T, Berger R, Dombret H, Fenaux P. 1990. Treatment of first relapse in acute promyelocytic leukaemia with all-trans retinoic acid. Lancet, 336: 1440~1441
Devaraj S G, Wang N, Chen Z, Chen Z, Tseng M, Barretto N, Lin R, Peters C J, Tseng C T, Baker S C, Li K. 2007. Regulation of IRF-3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus. J Biol Chem, 282(44): 32208~32221
Dijkers P F, Medemadagger R H, LammersJ J, Koenderman L, Coffer P J. 2000b. Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1. Curr Biol, 10: 1201~1204
DiPerna G, Stack J, Bowie A G, Boyd A, Kotwal G, Zhang Z. 2004. Poxvirus protein N1L targets the I-kappaB kinase complex, inhibits signaling to NF-kappaB by the tumor necrosis factor superfamily of receptors, and inhibits NF-kappaB and IRF3 signaling by toll-like receptors. J Biol Chem, 279(35): 36570~36578
Drexler H G. 1996. Expression of the FLT-3 receptor and response to FLT3 ligand by leukemic cells. Leukemia, 10: 588~599
Duronio V, Scheid M P, Ettinger S. 1998. Downstream signalling events regulated by phosphatidylinositol 3-kinase activity. Cell Signal, 10: 233~239
Easton R M, Cho H, Roovers K, Shineman D W, Mizrahi M, Forman M S, Lee V M, Birnbaum M J. 2005. Role for Akt3/protein kinase Bg in attainment of normal brain size. Mol Cell Biol, 25: 1869~1878
Ermoian R P, Furniss C S, Lamborn K R, Basila D, Berger M S, Gottschalk A R, Nicholas M K, Stokoe D, Haas-Kogan D A. 2002. Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival. Clin Cancer Res, 8: 1100~1106
Fenaux P, Wang Z Z, Degos L. 2007. Treatment of acute promyelocytic leukemia by retinoids. Curr Top Microbiol Immunol, 313: 101~128
Fernandes-Alnemri T, Yu J W, Datta P, Wu J, Alnemri E S. 2009. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature, 458: 509~13
Fingar D C, Richardson C J, Tee A R, Cheatham L, Tsou C, Blenis J. 2004. mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E. Mol Cell Biol, 24: 200~216
Fingar D C, Salama S, Tsou C, Harlow E, Blenis J. 2002. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev, 16: 1472~1487
Fire A, Xu S, Montgomery M K, Kostas S A, Driver S E, Mello C C. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 391: 806~811
Fitzgerald K A, McWhirter S M, Faia K L, Rowe D C, Latz E, Golenbock D T, Coyle A J, Liao S M, Maniatis T. 2003. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol, 4: 491~496
Flynn P J, Miller W J, Weisdorf D J, Arthur D C, Brunning R, Branda R F. 1983. Retinoic acid treatment of acute promyelocytic leukemia: in vitro and in vivo observations. Blood, 62: 1211~1217 for virus-triggered IFN-beta signaling. Mol Cell, 19: 727~740
Franke T F, Hornik C P, Segev L, Shostak G A, Sugimoto C. 2003. PI3K/Akt and apoptosis: size matters. Oncogene, 22: 8983~8998
Frauwirth K A, Riley J L, Harris M H, Frauwirth K A, Riley J L, Harris M H. 2002. The CD28 signaling pathway regulates glucose metabolism. Immunity, 16: 769~777
Fredericksen B L, Keller B C, Fornek J, Katze M G, Gale M Jr. 2008. Establishment and maintenance of the innate antiviral response to West Nile Virus involves both RIG-I and MDA5 signaling through IPS-1. J Virol, 82(2): 609~616
Friedman C S, O’Donnell M, Legarda-Addison D, Ng A, Cardenas W B, Yount J S, Moran T M, Basler C F, Komuro A, Horvath C M, Xavier R, Ting A T. 2008. Tumor suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. EMBO, Reports 9(9): 930~6
Friend C, Scher W, Holland J G, Sato T. 1971. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A, 68: 378~382
Furnari F B, Huang H J, Cavenee W K. 1998. The phosphoinositol phosphatase activity of PTEN mediates a serum-sensitive G1 growth arrest in glioma cells. Cancer Res, 58: 5002~5008
Furnari F B, Lin H, Huang H-J S, Cavenee W K. 1997.Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain. Proc Natl Acad Sci U S A, 94: 12479~12484
Gack M U, Shin Y C, Joo C H, Urano T, Liang C, Sun L. 2007. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature, 446: 916~20
Galanis E, Buckner J C, Maurer M J, Kreisberg J I, Ballman K, Boni J, Peralba J M, Jenkins R B, Dakhil S R, Morton R F, Jaeckle K A, Scheithauer B W, Dancey J, Hidalgo M, Walsh D J. 2005. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J Clin Oncol, 23: 5294~5304
Gee P, Chua P K, Gevorkyan J, Klumpp K, Najera I, Swinney D C, Deval J. 2008. Essential role of the N-terminal domain in the regulation of RIG-I ATPase activity. J Biol Chem, 283(14): 9488～9496
Gilliet M, Cao W, Liu Y J. 2008. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol, 8: 594~606
Gingras A C, Gygi S P, Raught B, Polakiewicz R D, Abraham RT, Hoekstra M F. 1999a. Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism. Genes Dev 13: 1422~1437
Gingras A C, Raught B, Gygi S P, Niedzwiecka A, Miron M, Burley S K, Polakiewicz R D, Wyslouch-Cieszynska A, Aebersold R, Sonenberg N. 2001. Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev, 15: 2852~2864
Gingras A C, Raught B, Sonenberg N. 1999b. eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu Rev Biochem, 68: 913~963
Gold M R, Duronio V, Saxena S P, Schrader J W, Aebersold R. 1994. Multiple cytokines activate phosphatidylinositol 3-kinase in hemopoietic cells: Association of the enzyme with various tyrosine-phosphorylated proteins. J Biol Chem, 269: 5403~5412
Gossen M, Buard H. 1992. Tight control of gene expression in man malian cells by Tetracycline responsive promoters. Proc Natl Acad Sci USA, 89(12): 5547~5551
Granville C A, Memmott R M, Gills J J, Dennis P A. 2006. Handicapping the race to develop inhibitors of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway. Clin Cancer Res, 12: 679~689
Grolleau A, Bowman J, Pradet-Balade B, Puravs E, Hanash S, Garcia-Sanz JA. 2002. Global and specific translational control by rapamycin in T cells uncovered by microarrays and proteomics. J Biol Chem 277: 22175~22184
Guo B, Cheng G. 2007. Modulation of the interferon antiviral response by the TBK1 ? IKKi adaptor protein TANK. J Biol Chem, 282: 11817~11826
Haasnoot J, de Vries W, Geutjes E J, Prins M, de Haan P, Berkhout B. 2007. The Ebola virus VP35 protein is a suppressor of RNA silencing. PLoS Pathog, 3: 794~803
Habjan M, Andersson I, Klingstrom J, Schumann M, Martin A, Zimmermann P, Wagner V, Pichlmair A, Schneider. 2008. Processing of genome 5′termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction. PLoS ONE, 3(4): 2032
Hacker H, Redecke V, Blagoev B, Kratchmarova I, Hsu L C, Wang G G, Kamps M P, Raz E, Wagner H, Hacker G, Mann M, Karin M. 2006. Specificity in toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature, 439: 204~7
Hahn-Windgassen A, Nogueira V, Chen C C, Skeen J E, Sonenberg N, Hay N. 2005. Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity. J Biol Chem, 280: 32081~32089
Hakki M, Geballe A P. 2005. Double-stranded RNA binding by human cytomegalovirus pTRS1. J Virol, 79(12): 7311~7318
Hanada M, Feng J, Hemmings B A. 2004. Structure, regulation and function of PKB/AKT– a major therapeutic target. Biochim Biophys Acta, 1697: 3~16
Harima Y, Sawada S, Nagata K, Sougawa M, Ostapenko V, Ohnishi T. 2001. Harris T E, Chi A, Shabanowitz J, Hunt D F, Rhoads R E, Lawrence Jr JC. 2006. mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin. EMBO J 25: 1659~1668
Hartmann C, Bartels G, Gehlhaar C, Holtkamp N, von Deimling A. 2005. PIK3CA mutations in glioblastoma multiforme. Acta Neuropathol, 109639~642
Haslam R J, Koide H B, Hemmings B A. 1993. Pleckstrin domain homology. Nature, 363: 309~310
Hay N, Sonenberg N. 2004. Upstream and downstream of mTOR. Genes Dev, 18: 1926~1945
He L-Z, Guidez F, Tribioli C, Peruzzi D, Ruthardt M, Zelent A, Pandolfi PP. 1998. Distinct interactions of PML-RARalpha and PLZF-RARalpha with co-repressors determine differential responses to RA in APL. Nat Genet, 18: 126~135
Hemmi H, Takeuchi O, Sato S, Yamamoto M, Kaisho T, Sanjo H, Kawai T, Hoshino K, Takeda K, Akira S. 2004. The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection. J Exp Med, 199: 1641~1650
Hennessy B T, Smith D L, Ram P T, Lu Y, Mills G B. 2005. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 4: 988~1004
Herbert T P, Fahraeus R, Prescott A, Lane D P, Proud C G. 2000. Rapid induction of apoptosis mediated by peptides that bind initiation factor eIF4E. Curr Biol, 10: 793~796
Hillestad LK. 1957. Acute promyelocytic leukemia. Acta Med Scand, 159:189~194
Holz M K, Ballif B A, Gygi S P, Blenis J. 2005. mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell, 123:569~580
Honda K, Takaoka A, Taniguchi T. 2006. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity, 25: 349~360
Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N, Taniguchi T. 2005. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature, 434: 772~777
Horman S, Vertommen D, Heath R, Neumann D, Mouton V, Woods A, Schlattner U, Wallimann T, Carling D, Hue L, Rider M H. 2006. Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinaseα-subunits in heart via hierarchical phosphorylation of Ser485/491. J Biol Chem, 281: 5335~5340
Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, Caffrey D R, Latz E, Fitzgerald K A. 2009. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature, 458: 514~8
Hornung V, Ellegast J, Kim S, Brzózka K, Jung A, Kato H, Poeck H, Akira S, Conzelmann K K, Schlee M, Endres S. 2006. 5’-Triphosphate RNA is the ligand for RIG-I. Science, 314: 994~997
Hresko R C, Mueckler M. 2005. mTOR/RICTOR is the Ser473 kinase for Akt/PKB in 3T3-L1 adipocytes. J Biol Chem, 280: 40406~40416
Hsu H, Huang J, Shu H B, Baichwal V, Goeddel D V. 1996. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity, 4(4): 387~396
Hu M C, Lee D F, Xia W, Golfman L S, Ou-Yang F, Yang J Y, Zou Y, Bao S, Hanada N, Saso H, Kobayashi R and Hung M C. 2004. IκB Kinase Promotes Tumorigenesis through Inhibition of Forkhead FOXO3a. Cell, 117: 225~237
Huang F, Adelman J, Jiang H, Goldstein N I, Fisher P B. 1999a. Identification and temporal expression pattern of genes modulated during irreversible growth arrest and terminal differentiation in human Huang F, Adelman J, Jiang H, Goldstein N I, Fisher P B. 1999b. Differentiation induction subtraction hybridization (DISH): an approach for cloning genes differentially expressed during growth arrest and Huang H, Regan K M, Wang F, Wang D, Smith D I, van Deursen J M, Tindall D J.. 2005. Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proc Natl Acad Sci USA, 102: 1649~1654
Huang J, Liu T, Xu LG, Chen D, Zhai Z, Shu H B. 2005. SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways. EMBO J, 24: 4018~28
Huang M E, Ye Y C, Chen S R, Chai J R, Lu J X, Zhoa L, Gu L J, Wang Z Y. 1988. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood, 72(2): 567~572
Huang M E, Ye Y C, Chen S R, Zhao J C, Gu L J, Cai J R, Zhao L, Xie J X, Wang Z Y. 1987. All-trans retinoic acid with or without low dose cytosine arabinoside in acute promyelocytic leukemia: report of 6 cases. Chin Med J. (Engl), 100: 949~953
Hutvágner G, Zamore P D. 2002. RNAi: nature abhors a double-strand. Curr Opin Genet Dev, 12: 225~232
Ihle N T, Paine-Murrieta G, Berggren M I, Baker A, Tate W R, Wipf P, Abraham R T, Kirkpatrick D L, Powis G. 2005. The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts. Mol Cancer Ther, 4: 1349~1357
Ikenoue T, Kanai F, Hikiba Y, Obata T, Tanaka Y, Imamura J, Ohta M, Jazag A, Guleng B, Tateishi K, Asaoka Y, Matsumura M, Kawabe T, Omata M. 2005. Functional analysis of PIK3CA gene mutations in human colorectal cancer. Cancer Res, 65: 4562~4567
Inoki K, Zhu T, Guan K L. 2003. TSC2 mediates cellular energy response to control cell growth and survival. Cell, 115: 577~590
Ishii K J, Coban C, Kato H, Takahashi K, Torii Y, Takeshita F. 2006. A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA. Nat Immunol, 7: 40~8
Ishii Ken J, Kawagoe Tatsukata, Koyama Shohei, Matsui Kosuke, Kumar Himanshu, Kawai Taro, Uematsu Satoshi, Takeuchi Osamu, Takeshita Fumihiko, Coban Cevayir, Akira Shizuo. 2008. TANK-binding kinase-1delineates innate and adaptive immune responses to DNA vaccines. Nature, 451: 725~729
Ishikawa H, Barber G N. 2008. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature, 455: 674~678
Janeway C A Jr, Medzhitov R. 2002. Innate immune recognition. Annu Rev Immunol, 20: 197~216
Jiang B H, Zheng J Z, Aoki M, Vogt P K. 2000. Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Proc Natl Acad Sci U S A, 97: 1749~1753
Joo C H, Shin Y C, Gack M, Wu L, Levy D, Jung J U. 2007. Inhibition of interferon regulatory factor 7 (IRF7)-mediated interferon signal transduction by the Kaposi's sarcoma-associated herpesvirus viral IRF homolog vIRF3. J Virol, 81(15): 8282~8292
Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, Xin K Q, Ishii K J, Kawai T, Akira S, Suzuki K, Okuda K. 2007. The Atg5-Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci USA, 104: 14050~5
Kakizuka A, Miller W H, Umesono K ,Warrell RP, Frankel S R, Murty V V, Dmitrovsky E, Evans RM. 1991. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell, 66: 663~674
Kang D C, Gopalkrishnan R V, Lin L, Randolph A, Valerie K, Pestka S, Fisher P B. 2004. Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon responsive apoptosis-inducing gene. Oncogene, 23: 1789~800
Kang D C, Gopalkrishnan R V, Wu Q, Jankowsky E, Pyle A M, Fisher P B. 2002. mda-5: An interferon -inducible putative RNA helicase with double-stranded RNA dependent ATPase activity and melanoma growth-suppressive properties. Proc Natl Acad Sci USA, 99: 637~642
Kang S, Bader A G, Vogt P K. 2005. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci USA, 102: 802~807
Kaplan D R, Whitman M, Schaffhausen B, Pallas D C, White M, Cantley L, Roberts T M. 1987. Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity. Cell, 50: 1021~1029
Kato H, Sato S, Yoneyama M, Yamamoto M, Uematsu S, Matsui K, Tsujimura T, Takeda K, Fujita T, Takeuchi O, Akira S. 2005. Cell type-specific involvement of RIG-I in antiviral response. Immunity, 23(1): 19~28
Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K. 2006. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature, 441: 101~5
Kawai T, Akira S. 2008. Toll-like receptor and RIG-I-like receptor signaling. Ann N Y Acad Sci, 1143: 1~20
Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii K J, Takeuchi O, Akira S. 2005. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol, 6(10): 981~988
Kayagaki N, Phung Q, Chan S, Chaudhari R, Quan C, O’Rourke K M, Eby M, Pietras E, Cheng G, Bazan J F, Zhang Z, Arnott D, Dixit V M. 2007. DUBA: a deubiquitinase that regulates type I interferon production. Science, 318: 1628~32
Khwaja A, Lehmann K, Marte B M, Downward J. 1998. Phosphoinositide 3-kinase induces scattering and tubulogenesis in epithelial cells through a novel pathway. J Biol Chem, 273: 18793~18801
Knobbe C B, Reifenberger G. 2003. Genetic alterations and aberrant expression of genes related to the phosphatidyl-inositol-3′-kinase/protein kinase B(Akt) signal transduction pathway in glioblastomas. Brain Pathol, 13: 507~518
Kohno T, Takahashi M, Manda R, Yokota J. 1998. Inactivation of the PTEN/MMAC1/TEP1 gene in human lung cancers. Genes Chromosomes Cancer, 22: 152~156
Komuro A, Horvath C M. 2006. RNA- and virusindependent inhibition of antiviral signaling by RNA helicase LGP2. J Virol, 80: 12332~12342
Kops G J, de Ruiter N D, De Vries-Smits A M, Powell D R, Bos J L, Burgering B M. 1999. Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature, 398:630~634
Kornblau S M, Womble M, Qiu Y H, Jackson C E, Chen W, Konopleva M. 2006. Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia. Blood, 108: 2358~2365
Kovacsovics M, Martinon F, Micheau O, Bodmer J L, Hofmann K, Tschopp J. 2002. Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation. Curr Biol, 12(10): 838~843
Krieg A M. 2007. The toll of too much TLR7. Immunity, 27: 695~7
Laleh Shayesteh, Yiling Lu, Wen-Lin Kuo, Russell Baldocchi, Tony Godfrey, Colin Collins, Daniel Pinkel, Bethan Powell, Gordon B Mills, Joe W Gray. 1999. PIK3CA is implicated as an oncogene in ovarian cancer. Nature Genet, 21: 99~102
Lam P K, To E W, Chan E S, Liew C T, Lung I W, King W K. 2001. In vitro inhibition of head and neck cancer-cell growth by human recombinant interferon-alpha and 13-cis-retionic acid. Br J Biomed Sci, 58: 226~229
Lee E G, Boone D L, Chai S, Libby S L, Chien M, Lodolce J P, Ma A. Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science 2000, 289: 2350~4
Lee J W, Soung Y H, Kim S Y, Lee H W, Park W S, Nam S W, Kim S H, Lee J Y, Yoo N J, Lee S H. 2005. PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene, 24: 1477~1480
Lee S, Comer F I, Sasaki A, McLeod I X, Duong Y, Okumura K, Yates J R 3rd, Parent C A, Firtel R A. 2005. TOR complex 2 integrates cell movement during chemotaxis and signal relay in Dictyostelium. Mol Biol Cell, 16: 4572~4583
LeeY, Kim M, Han J. 2004. MicroRNA genes are transcribed by RNA polymerase II. EMBO J, 23(20): 4051~4060
Lefort S, Soucy-Faulkner A, Grandvaux N, Flamand L. 2007. Binding of Kaposi's sarcoma-associated herpesvirus K-bZIP to interferon-responsive factor 3 elements modulates antiviral gene expression. J Virol 81(20): 10950~10960
Levine D A, Bogomolniy F, Yee C J, Lash A, Barakat R R, Borgen P I, Boyd J. 2005. Frequent mutation of the PIK3CA gene in ovarian and breast cancers. Clin Cancer Res, 11: 2875~2878
Li G, Robinson G W, Lesche R, Martinez-Diaz H, Jiang Z, Rozengurt N, Wagner K U, Wu D C, Lane T F, Liu X, Hennighausen L,Wu H. 2002. Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development, 129: 4159~4170
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang S I, Puc J, McCombie. 1997. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 275: 1943~1947
Li V S, Wong C W, Chan T L, Chan A S, Zhao W, Chu K M, So S, Chen X, Yuen S T, Leung S Y. 2005 .Mutations of PIK3CA in gastric adenocarcinoma. BMC Cancer, 5: 29
Li X D, Sun L, Seth R B, Pineda G, Chen Z J. 2005. Hepatitis C virus protease NS3 ? 4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci USA, 102: 17717~17722
Liaw D, Marsh D J, Li J, Dahia P L, Wang S I, Zheng Z, Bose S, Peacocke M .1997. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet, 16: 64~67
Lin R, Genin P, Mamane Y, Sgarbanti M, Battistini A, Harrington W J. 2001. HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators. Oncogene, 20(7): 800~811
Lin R, Lacoste J, Nakhaei P, Sun Q, Yang L, Paz S, Wilkinson P, Julkunen I, Vitour D, Meurs E, Hiscott J. 2006. Dissociation of a MAVS/IPS-1/VISA/Cardif-IKKepsilon molecular complex from the mitochondrial outer membrane by hepatitis C virus NS3-4A proteolytic cleavage. J Virol, 80(12): 6072~6083
Lin R, Yang L, Nakhaei P, Sun Q, Sharif-Askari E, Julkunen I, Hiscott J. 2006. Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. J Biol Chem, 281: 2095~103
Lindner D J, Borden E C, Kalvakolanu D V. 1997. Synergistic antitumor effects of a combination of interferons and retinoic acid on human tumor cells in vitro and in vivo. Clin Cancer Res, 3: 931~937
Lingen M W, Polverini P J, Bouck N P. 1998. Retinoic acid and interferon alpha act synergistically as antiangiogenic and antitumor agents against human head and neck squamous cell carcinoma. Cancer Res, 58: 5551~5558
Lippman, S M, Parkinson D R, Itri L M, Weber R S, Schantz S P, Ota D M, Schusterman M A, Krakoff I H, Gutterman J U, Hong W K. 1992. 13-cis-Retinoic acid and interferon alpha-2a: effective combination therapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst, 84: 235~241
Liu T X, Zhang J W, Tao J, Zhang R B, Zhang Q H, Zhao C J, Tong J H, Lanotte M, Waxman S, Chen S J, Mao M, Hu G X, Zhu L, Chen Z. 2000. Gene expression networks underlying retinoic acid-induced differentiation of acute promyelocytic leukemia cells. Blood, 96(4): 1496~1504
Liu Y C, Penninger J, Karin M. 2005. Immunity by ubiquitylation: a reversible process of modification. Nat Rev Immunol, 5(12): 941~952
Lo-Coco F, Ammatuna E. 2006. The biology of acute promyelocytic leukemia and its impact on diagnosis and treatment. Hematol (Am Soc Hematol Educ Program), 156~161
Loo Y M, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, Akira S, Gill M A, García -Sastre A, Katze M G, Gale M Jr. 2008. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol, 82(1): 335~345
Lu L L, Puri M, Horvath C M, Sen G C. 2008. Select paramyxoviral V proteins inhibit IRF3 activation by acting as alternative substrates for inhibitor of kappaB kinase epsilon (IKKe)/TBK1. J Biol Chem, 283(21): 14269~14276
Lynch M, Fitzgerald C, Johnston K A, Wang S, Schmidt E V. 2004. Activated eIF4E-binding protein slows G1 progression and blocks transformation by c-myc without inhibiting cell growth. J Biol Chem, 279: 3327~3339
Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi P P. 2005. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell, 121: 179~193
Maehama T, Dixon J E. 1998. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem, 273: 13375~13378
Mamane Y, Petroulakis E, LeBacquer O, Sonenberg N. 2006. MTOR, translation initiation and cancer. Oncogene, 25:6416~22
Marsh D J, Coulon V, Lunetta K L, Marsh D J, Coulon V, Lunetta K L, Rocca-Serra P, Dahia P L M, Zheng Z, Liaw D. 1998. Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet, 7: 507~515
Martinon F, Tschopp J. 2007. Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ, 14: 10~22
Massad L S, Turyk M E, Bitterman P, Wilbanks G D. 1996. Interferon-alpha and all-trans-retinoic acid reversibly inhibit the in vitro proliferation of cell lines derived from cervical cancers. Gynecol Oncol, 60: 428~434
Matsuzaki H, Daitoku H, Hatta M, Tanaka K, Fukamizu A. 2003. Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation. Proc Natl Acad Sci USA, 100: 11285~11290
McManus E J, Collins B J, Ashby P R, Prescott A R, Murray-Tait V, Armit L J, Arthur J S, Alessi D R. 2004. The in vivo role of PtdIns(3,4,5)P3 binding to PDK1 PH domain defined by knockin mutation. EMBO J, 23: 2071~2082
McWhirter S M, Fitzgerald K A, Rosains J, Rowe D C, Golenbock D T, Maniatis T. 2004. IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts. Proc Natl Acad Sci USA, 101: 233~8
Medema R H, Kops G J, Bos J L, Burgering B M. 2000. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 404: 782~787
Medzhitov R. 2001. Toll-like receptors and innate immunity. Nature Rev Immunol, 1(2): 135~145
Meijer A J, Codogno P. 2004. Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol, 36:2445~62
Melroe G T, Silva L, Schaffer P A, Knipe D M. 2007. Recruitment of activated IRF-3 and CBP/p300 to herpes simplex virus ICPO nuclear foci: potential role in blocking IFN-beta induction. Virology 360(2): 305~321
Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J. 2005. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature, 437: 1167~72
Michallet M C, Meylan E, Ermolaeva M A, Vazquez J, Rebsamen M, Curran J, Poeck H, Bscheider M, Hartmann G, K?nig M, Kalinke U, Pasparakis M, Tschopp J. 2008. TRADD protein is an essential component of the RIG-like helicase antiviral pathway. Immunity, 28: 651~661
Micheau O, Tschopp J. 2003. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell, 114: 181~190
Min Y H, Eom J I, Cheong J W, Maeng H O, Kim J Y, Jeung H K. 2003. Constitutive phosphorylation of Akt/PKB protein in acute myeloid leukemia: its significance as a prognostic variable. Leukemia, 17: 995~997
Modur V, Nagarajan R, Evers B M, Milbrandt J. 2002. FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. J Biol Chem, 277: 47928~47937
Moore C B, Bergstralh D T, Duncan J A, Lei Y, Morrison T E, Zimmermann A G, Heise M T, Chen Z, Ting J P. 2008. NLRX1 is a regulator of mitochondrial antiviral immunity. Nature, 451: 573~7
Mothe-Satney I, Yang D, Fadden P, Haystead T A J, Lawrence J C. 2000b. Multiple mechanisms control phosphorylation of PHAS-I in five (S/T)P sites that govern translational repression. Mol Cell Biol, 20: 3558~3567
Musto P, Sajeva M R, Sanpaolo G, D’Arena G, Scalzulli P R, Carotenuto M. 1997. All-trans-retinoic acid in combination with alpha-interferon and dexamethasone for advanced multiple myeloma. Haematologica, 82: 354~356
Mutation of the PTEN gene in advanced cervical cancer correlated with tumor progression and poor outcome after radiotherapy. Int J Oncol, 18: 493~497
Myers M P, Pass I, Batty I H, Van der Kaay J, Stolarov J P, Hemmings B A, Wigler M H, Downes C P, Tonks N K. 1998. The lipid phosphatase activity of PTEN is critical for its tumor supressor function. Proc Natl Acad Sci U S A, 10; 95(23): 13513~13518
Myers M P, Stolarov J P, Eng C, Li J, Wang S I, Wigler M H, Parsons R, Tonks N K. 1997. P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc Natl Acad Sci U S A, 94: 9052~9057
Nakatani K, Thompson D A, Barthel A, Sakaue H, Liu W, Weigel R J, Roth R A. 1999. Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines. J Biol Chem, 274: 21528~21532
Nakayama K, Nakayama N, Kurman R J, Cope L, Pohl G, Samuels Y, Velculescu V E, Wang T L, Shih I. 2006. Sequence mutations and amplification of PIK3CA and AKT2 genes in purified ovarian serous neoplasms. Cancer Biol Ther, 5: 779~785
Nervi C, Ferrara F F, Fanelli M, Rippo M R, Tomassini B, Ferrucci P F, Ruthardt M. 1998. Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein. Blood, 92: 2244~2251
Neznanov N, Chumakov K M, Neznanova L, Almasan A, Banerjee A K., Gudkov A V. 2005. Proteolytic cleavage of the p65-RelA subunit of NF-kappaB during poliovirus infection. J Biol Chem, 280(25): 24153~24158
Ngo V N, Davis R E, Lamy L. 2006. A loss-of-function RNA interference screen for molecular targets in cancer. Nature, 41: 106~110
Nilsson B. 1984. Probable in vivo induction of differentiation by retinoic acid of promyelocytes in acute promyelocytic leukaemia. Br J Haematol, 57:365~371
NLRX1 is a mitochondrial NOD-like receptor that amplifies NF-kappaB and JNK pathways by inducing reactive oxygen species production. EMBO Rep, 9: 293~300
Nojima H, Tokunaga C, Eguchi S, Oshiro N, Hidayat S, Yoshino K, Hara K, Tanaka N, Avruch J, Yonezawa K. 2003. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem, 278: 15461~15464
O’Neill L A. 2008. The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol Rev, 226: 10~8
Obsil T, Ghirlando R, Anderson D E, Hickman A B, Dyda F. 2003. Two 14-3-3 binding motifs are required for stable association of Forkhead transcription factor FOXO4 with 14-3-3 proteins and inhibition of DNA binding. Biochemistry, 42: 15264~15272
Oganesyan G, Saha S K, Guo B, He J Q, Shahangian A, Zarnegar B, Perry A, Cheng G. 2006. Critical role of TRAF3 in the toll-like receptor-dependent and -independent antiviral response. Nature, 439: 208~11
Ogura Y, Inohara N, Benito A, Chen F F, Yamaoka S, Nunez G. 2001. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kB. J Biol Chem, 276(7): 4812~4818
Oh J S, Kucab J E, Bushel P R, Martin K, Bennett L, Collins J, DiAugustine R P, Barrett J C, Afshari C A, Dunn S E. 2002. Insulin-like growth factor-1 inscribes a gene expression profile for angiogenic factors and cancer progression in breast epithelial cells. Neoplasia, 4: 204~217
Okumura A, Alce T, Lubyova B, Ezelle H, Strebel K, Pitha P M. 2008. HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation. Virology, 373(1): 85~97
Opipari A W J, Boguski M S, Dixit V M. 1990. The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. J Biol Chem, 265: 14705~8
Otsuka M, Kato N, Moriyama M, Taniguchi H, Wang Y, Dharel N, Kawabe T, Omata M. 2005.Interaction between the HCV NS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses. Hepatology 41(5): 1004~1012
Papapetropoulos A, Fulton D, Mahboubi K., Kalb R G, O'Connor D S, Li F, Altieri D C, Sessa W C. 2000. Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway. J Biol Chem, 275: 9102~9105
Pedrero J M, Carracedo D G, Pinto C M, Zapatero A H, Rodrigo J P, Nieto C S, Gonzalez M V. 2005. Frequent genetic and biochemical alterations of the PI3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma. Int J Cancer, 114: 242~248
Perrot V, Rechler M M. 2005. The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. Mol Endocrinol, 19: 2283~2298
Perry A K, Chow E K, Goodnough J B, Yeh W C, Cheng G. 2004. Differential requirement for TANK -binding kinase-1 in type I interferon responses to toll-like receptor activation and viral infection. J Exp Med, 199: 1651~1658
Peso del L, Gonzalez-Garcia M, Page C, del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez. 1997. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science, 278: 687~689
Peterson TR, Sabatini D M. 2005. eIF3: a connecTOR of S6K1 to the translation preinitiation complex. Mol Cell, 20: 655~657
Pichlmair A, Schulz O, Tan C P, Naslund T I, Liljestrom P, Weber F, Reis e Sousa C. 2006. RIG-I mediated antiviral responses to single-stranded RNA bearing 5’-phosphates. Science, 314: 997~1001
Pierce G B Jr, Verney E L. 1961. An in vitro and in vivo study of differentiation in teratocarcinoma. Cancer, 14: 1017~1029
Pippig D A, Hellmuth J C, Cui S, Kirchhofer A, Lammens K, Lammens A, Schmidt A, Rothenfusser S, Hopfner, K P. 2009. Theregulatory domain of the RIG-I family ATPase LGP2 senses double-stranded Plas D R, Thompson C B. 2003. Akt activation promotes degradation of tuberin and FOXO3a via the proteasome. J Biol Chem, 278: 12361~12366
Plotch S J, Bouloy M, Ulmanen I. Krug R M. 1981. A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell, 23(3): 847~858
Plumet S, Herschke F, Bourhis J M, Valentin H, Longhi S, Gerlier D. 2007. Cytosolic 5’-triphosphate ended viral leader transcript of measles virus as activator of the RIG I-mediated interferon response. PLoS ONE, 2: 279
Polunovsky V A, Gingras A C, Sonenberg N, Peterson M, Tan A, Rubins J B, Manivel J C, Bitterman P B. 2000. Translational control of the antiapoptotic function of Ras. J Biol Chem, 275: 24776~24780
Potter J A, Randall R E, Taylor G L. 2008. Crystal structure of human IPS-1 ? MAVS ? VISA ? Cardif caspase activation recruitment domain. BMC Struct Biol, 8: 11
Proud C G. 2005. The eukaryotic initiation factor 4E-binding proteins and apoptosis. Cell Death Differ, 12: 541~546
Pullen N, Dennis P B, Andjelkovic M, Dufner A, Kozma S C, Hemmings B A, Thomas G. 1998. Phosphorylation and activation of p70s6k by PDK1. Science, 279: 707~710
Raffioni S, Bradshaw RA. 1992. Activation of phosphatidylinositol 3-kinase by epidermal growth factor, basic fibroblast growth factor, and nerve growth factor in PC12 pheochromocytoma cells. Proc Natl Acad Sci U S A, 89: 9121~9125
Ramaswamy S, Nakamura N, Sansal I, Bergeron L, Sellers W R. 2002. A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR. Cancer Cell, 2: 81~91
Rao P, Mufson R A. 1995. A membrane proximal domain of the human interleukin-3 receptor beta c subunit that signals DNA synthesis in NIH 3T3 cells 1995 specifically binds a complex of Src and Janus family tyrosine kinases and phosphatidylinositol 3-kinase. J Biol Chem, 270: 6886~6893
Rebsamen M, Meylan E, Curran J, Tschopp J. 2008. The antiviral adaptor proteins Cardif and Trif are processed and inactivated by caspases. Cell Death Differ, 15(11): 1804~1811
Redner RL. 2002. Variations on a theme: the alternate translocations in APL. Leukemia, 16: 1927~1932
Rena G., Prescott A R, Guo S, Cohen P, Unterman T G. 2001. Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in regulating 14-3-3 binding, transactivation and nuclear targetting. Biochem J, 354: 605~612
Ribeiro R C, Rego E. 2006. Management of APL in developing countries: epidemiology, challenges and opportunities for international collaboration. Hematol (Am Soc Hematol Educ Program), 162~168 RNA. Nucleic Acids Res, 37: 2014~25
Roberts T L, Idris A, Dunn J A, Kelly G M, Burnton C M, Hodgson S, Hardy L L, Garceau V, Sweet M J, Ross I L, Hume D A, Stacey K J. 2009. HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science, 323: 1057~60
Rothenfusser S, Goutagny N, DiPerna G, Gong M, Monks B G, Schoenemeyer A, Yamamoto M, Akira S, Fitzgerald K A. 2005. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. J Immunol, 175:5260~5268
Rowley J D, Golomb H M, Dougherty C. 1977. 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia. Lancet, 1: 549~550
Ruderman N B, Kapeller R, White M F, Cantley L C. 1990. Activation of phosphatidylinositol 3-kinase by insulin. Proc Natl Acad Sci U S A, 87: 1411~1415
Runde V, Aul C, Sudhoff T, Heyll A, Schneider W. 1992. Retinoic acid in the treatment of acute promyelocytic leukemia: inefficacy of the 13-cis isomer and induction of complete remission by the all-trans isomer complicated by thromboembolic events. Ann Hematol, 64: 270~272
Ryzhakov G, Randow F. 2007. SINTBAD, a novel component of innate antiviral immunity, shares a TBK1 -binding domain with NAP1 and TANK. EMBO J, 26: 3180~3190
Saal L H, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu J S, Malmstr?m P O, Mansukhani M, Enoksson J, Hibshoosh H, Borg A, Parsons R. 2005. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res,65: 2554~2559
Sachs L. 1978. Control of normal cell differentiation and the phenotypic reversion of malignancy in myeloid leukaemia. Nature, 274: 535~539
Saha S K, Pietras E M, He J Q, Kang J R, Liu S Y, Oganesyan G, Shahangian A, Zarnegar B, Shiba T L, and Cheng G. 2006. Regulation of antiviral responses by a direct and specific interaction between TRAF3 and cardif. EMBO J, 25: 3257~63
Saira K, Zhou Y, Jones C. 2007. The infected cell protein O encoded by bovine herpesvirus 1 (bICPO) induces degradation of interferon response factor 3 and consequently, inhibits beta interferon promoter activity. J Virol, 81(7): 3077~3086
Saito T, Hirai R, Loo Y M, Owen D, Johnson C L, Sinha S C, Akira S, Fujita T, Gale M Jr. 2007. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci USA, 104: 582~587
Saitoh T, Tun-Kyi A, Ryo A, Yamamoto M, Finn G, Fujita T, Akira S, Yamamoto N, Lu K P, Yamaoka S. 2006. Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1. Nat Immunol, 7: 598~605
Saitoh T, Yamamoto M, Miyagishi M, Taira K, Nakanishi M, Fujita T, Akira S, Yamamoto N, Yamaoka S. 2005. A20 is a negative regulator of IFN regulatory factor 3 signaling. J Immunol, 174: 1507~12
Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell S M, Riggins G J, Willson J K, Markowitz S, Kinzler K W, Vogelstein B, Velculescu VE. 2004. High frequency of mutations of the PIK3CA gene in human cancers. Science, 304: 554
Sansal I, Sellers W R. 2004. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol, 22: 2954~2963
Sanz M A, Jarque I, Martín G, Lorenzo I, Martínez J, Rafecas J, Pastor E, Sayas M J, Sanz G, Gomis F. 1988. Acute promyelocytic leukemia: therapy results and prognostic factors. Cancer, 61: 7~13
Sarbassov D D, Ali S M, Kim D H, Guertin D A, Latek R R, Erdjument-Bromage H, Tempst P, Sabatini D M. 2004. Rictor, a novel binding partner of mTOR, defines a rapamycininsensitiveand raptor-independent pathway that regulates the cytoskeleton. Curr Biol, 14: 1296~1302
Sarbassov D D, Guertin D A, Ali S M, Sabatini D M. 2005. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science, 307: 1098~1101
Sasai M, Shingai M, Funami K, Yoneyama M, Fujita T, Matsumoto M, Seya T. 2006. NAK-associated protein 1 participates in both the TLR3 and the cytoplasmic pathways in type I IFN induction. J Immunol, 177: 8676~8683
Schalm S S, Blenis J. 2002. Identification of a conserved motif required for mTOR signaling. Curr Biol, 12: 632~639
Schalm S S, Fingar D C, Sabatini D M, Blenis J. 2003. TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr Biol, 13:797~806
Schmidt M, Fernandez de Mattos S, van der Horst A, Klompmaker R, Kops G J, Lam E W, Burgering B M, Medema R H. 2002. Cell cycle inhibition by FoxO forkhead
Schroder M, Baran M, Bowie A G. 2008. Viral targeting ofDEADbox protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J, 27(15): 2147~2157
Schubert D, Humphreys S, Jacob F, de Vitry F. 1971. Induced differentiation of a neuroblastoma. Dev Biol, 25: 514~546
Schulze-Bergkamen H, Fleischer B, Schuchmarm M. 2006. Suppression of Mcl-l via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction. BMC Cancer, 6(10):232
Seoane J, Le H V, Shen L, Anderson S A, Massague, J. 2004. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell, 117: 211~223
Seth R B, Sun L, Ea C K, Chen Z J. 2005. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell, 122: 669~682
Shahbazian D, Roux P P, Mieulet V, Cohen M S, Raught B, Taunton J. 2006. The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity. EMBO J, 25: 2781~2791
Sharma S, tenOever B R, Grandvaux N, Zhou G P, Lin R, Hiscott J. 2003. Triggering the interferon antiviral response through an IKK-related pathway. Science, 300: 1148~51
Shaw R J, Bardeesy N, Manning B D, Lopez L, Kosmatka M, DePinho R A, Cantley L C .2004. The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell, 6: 91~99
Shayesteh L, Lu Y, Kuo W L, Baldocchi R, Godfrey T, Collins C, Pinkel D, Powell B, Mills G B, Gray J W. 1999. PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet, 21: 99~102
Smith E J, Marie I, Prakash A, Garcia-Sastre A, Levy D E. 2001. IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein. J Biol Chem, 276(12): 8951~8957
Soulat D, Burckstummer T ,Westermayer S, Goncalves A, Bauch A, Stefanovic A, Hantschel O, Bennett K L, Decker T, Superti-furga G. 2008. The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response. EMBO J, 27(15): 2135~2146
Staal S P. 1987. Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci U S A, 84: 5034~5037
Steck P A, Pershouse M A, Jasser S A, Yung W K, Lin H, Ligon A H, Langford L A, Baumgard M L, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng D H, Tavtigian S V. 1997. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet, 15: 356~362
Steelman L S, Bertrand F E, McCubrey J A. 2004. The complexity of PTEN: mutation, marker and potential target for therapeutic intervention. Expert Opin Ther Targets, 8: 537~550
Stetson D B, Medzhitov R. 2006. Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. Immunity, 24: 93~103
Sujobert P, Bardet V, Cornillet-Lefebvre P, Hayflick J S, Prie N, Verdier F. 2005. Essential role for the p110δisoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia. Blood, 106: 1063~1066
Sun Q, Sun L, Liu H H, Chen X, Seth R B. 2006. The specific and essential role of MAVS in antiviral innate immune responses. Immunity, 24: 633~642
Suzuki A, de la Pompa J L, Stambolic V, Elia A J, Sasaki T, del B B, Ho A I, Wakeham A, Itie A, Khoo W, Fukumoto M, Mak T W. 1998. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol, 8: 1169~1178
Tait S W, Reid E B, Greaves D R, Wileman T E, Powell P P. 2000. Mechanism of inactivation of NF-kappa B by a viral homologue of I kappa b alpha. Signal-induced release of ikappa b alpha results in binding of the viral homologue to NF-kappa B. J Biol Chem, 275(44): 34656~34664
Takahashi K, Kawai T, Kumar H, Sato S, Yonehara S, Akira S. 2006. Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded RNA. J Immunol, 176: 4520~4524
Takahasi K, Yoneyama M, Nishihori T, Hirai R, Kumeta H, Narita R, Gale M Jr, Inagaki F, Fujita T. 2008. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. Mol Cell, 29: 428~40
Takaishi H, Konishi H, Matsuzaki H, Ono Y, Shirai Y, Saito N, Kitamura T, Ogawa W, Kasuga M, Kikkawa U, Nishizuka Y. 1999. Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B. Proc Natl Acad Sci USA, 96: 11836~11841
Takaoka A, Wang Z C, Choi M K, Yanai H, Negishi H, Ban T, Lu Y, Miyagishi M, Kodama T, Honda K, Ohba Y, Taniguchi T. 2007. DAI (DLM-1 ? ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature, 448: 501~505
Tang E D, Nunez G., Barr F G, Guan K L. 1999. Negative regulation of the forkhead transcription factor FKHR by Akt. J Biol Chem, 274: 16741~16746
Tattoli I, Carneiro L A, Jehanno M, Magalhaes J G, Shu Y, Philpott D J, Arnoult D, Girardin S E. 2008.
Tee A R, Blenis J. 2005. mTOR, translational control and human disease. Semin Cell Dev Biol, 16: 29~37 terminal differentiation in human melanoma cells. Gene, 236: 125~131
Thomas C C, Deak M, Alessi D R, van Aalten D M. 2002. High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate. Curr Biol, 12: 1256~1262
Thompson J E, Thompson C B. 2004. Putting the rap on Akt. J Clin Oncol, 22:4217~4226
Ting J P, Willingham S B, Bergstralh D T. 2008. NLRs at the intersection of cell death and immunity. Nat Rev Immunol, 8: 372~9
Tran H, Brunet A, Grenier J M, Datta S R, Fornace A J, DiStefano P S, Chiang L W, Greenberg M E. 2002. DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Science, 296: 530~534
Tran H, Brunet A, Griffith E C, Greenberg M E. 2003. The many forks in FOXO’s road. Sci STKE 172: Uematsu S, Akira S. 2007. Toll-like receptors and type I interferons. J Biol Chem, 282: 15319~23
Valchanova R S, Picard-Maureau M, Budt M, Brune W. 2006. Murine cytomegalovirus m142 and m143 are both required to block protein kinase R mediated shutdown of protein synthesis. J Virol, 80(20): 10181~10190
Venkataraman T, Valdes M, Elsby R, Kakuta S, Caceres G, Saijo S, Iwakura Y, Barber G N. 2007. Loss of DExD ? H box RNA helicase LGP2 manifests disparate antiviral responses. J Immunol, 178: 6444 ~ 6455
Vivanco I, Sawyers C L. 2002. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer, 2: 489~501
Vogt P K, Jiang H, Aoki M. 2005. Triple layer control: phosphorylation, acetylation and ubiquitination of FOXO proteins. Cell Cycle, 4: 908~913
vom Baur E, Zechel C, Heery D, Heine M J, Garnier J M, Vivat V, Le Douarin B, Gronemeyer H, Chambon P, Losson R. 1996. Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1. EMBO J, 15: 110~124
Wang X, Beugnet A, Murakami M, Yamanaka S, Proud C G. 2005. Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins. Mol Cell Biol, 25: 2558~2572
Wang Y Y, Li L, Han K J, Zhai Z, Shu H B. 2004. A20 is a potent inhibitor of TLR3- and Sendai virus -induced activation of NF-kappaB and ISRE and IFN-beta promoter. FEBS Lett, 576: 86~90
Wang Y, Helland A, Holm R, Kristensen G. B, Borresen-Dale A L. 2005. PIK3CA mutations in advanced ovarian carcinomas. Hum Mutat, 25: 322
Wang Y, Zhang H X, Sun Y P, Liu Z X, Liu X S, Wang L, Lu S Y, Kong H, Liu Q L, Li X H, Lu Z Y, Chen S J, Chen Z, Bao S S, Dai W, Wang Z G. 2007. Rig-I?/? mice develop colitis associated with downregulation of G alpha i2. Cell Res, 17: 858~68
Wang Z Y, Sun G L, Lu J X, Gu L J, Huang M E, Chen S R. 1990. Treatment of acute promyelocytic leukemia with all-trans retinoic acid in China. Nouv Rev Fr Hematol, 32: 34~36
Warrell R P, Frankel S R, Miller W H, Scheinberg D A, Itri L M, Hittelman W N, Vyas R, Andreeff M, Tafuri A, Jakubowski A. 1991. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). New Engl J Med, 324: 1385~1393
Wendel H G, De Stanchina E, Fridman J S, Malina A, Ray S, Kogan S, Cordon-Cardo C, Pelletier J, Lowe S W. 2004. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature, 428:332~7
Wertz I E, O’Rourke K M, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone D L, Ma A, Koonin E V, Dixit V M. 2004. Deubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature, 430: 694~9
Whiteman E L, Cho H, Birnbaum M J. 2002. Role of Akt/protein kinase B in metabolism. Trends Endocrinol Metab, 13: 444~451
Willment J A, Brown G D. 2008. C-type lectin receptors in antifungal immunity. Trends Microbiol, 16: 27~32
Wullschleger S, Loewith R, Hall M N. 2006. TOR signaling in growth and metabolism. Cell, 124: 471~484
Xia C, Meng Q, Cao Z, Shi X, Jiang B H. 2006. Regulation of angiogenesis and tumor growth by p110 alpha and AKT1 via VEGF expression. J Cell Physiol, 209: 56~66
Xiang Y, Condit R C, Vijaysri S, Jacobs B, Williams B R., Silverman R H. 2002. Blockade of interferon induction and action by the E3L double-stranded RNA binding proteins of vaccinia virus. J Virol, 76(10): 5251~5259
Xu L G, Wang Y Y, Han K J, Li L Y, Zhai Z, Shu H B. 2005. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell, 19: 727~40
Xu Q, Simpson S E, Scialla T J, Bagg A, Carroll M. 2003. Survival of acute myeloid leukemia cells requires PI3 kinase activation. Blood, 102: 972~980
Yamamoto S, Tomita Y, Hoshida Y, Morooka T, Nagano H, Dono K, Umeshita K, Sakon M, Ishikawa O, Ohigashi H, Nakamori S, Monden M, Aozasa K. 2004. Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma. Clin Cancer Res, 10: 2846~2850
Yang H, Zhao R, Yang H Y, Lee M H. 2005a. Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity. Oncogene, 24: 1924~1935
Yang Y, Liang Y, Qu L, Chen Z, Yi M, Li K, Lemon S M. 2007. Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor. Proc Natl Acad Sci U S A, 104(17): 7253~7258
Yoneyama M, Fujita T. 2008. Structural mechanism of RNA recognition by the RIGI-like receptors. Immunity, 29(2): 178~181
Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M Jr, Akira S, Yonehara S, Kato A, Fujita T. 2005. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA-5, and LGP2 in antiviral innate immunity. Immunol, 175(5): 2851~2858
Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T. 2004. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol, 5(7): 730~737
Zacchi P, Gostissa M, Uchida T, Salvagno C, Avolio F, Volinia S, Ronai Z, Blandino G, Schneider C, Del Sal G. 2002. The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults. Nature, 419: 853~7
Zeng Y W, agner E J, Cullen B R. 2002. Both natural and designed microRNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell, 9:1327
Zhang M, Wu X, Lee A J, Jin W, Chang M, Wright A, Imaizumi T, Sun S C. 2008. Regulation of IKK related kinases and antiviral responses by tumor suppressor CYLD. J Biol Chem, 283(27): 18621~6
Zhang N N, Shen S H, Jiang L J, Zhang W, Zhang H X, Sun Y P, Li X Y, Huang Q H, Ge B X, Chen S J, Wang Z G, Chen Z, Zhu J. 2008. RIG-I plays a critical role in negatively regulating granulocytic proliferation. Proc Natl Acad Sci USA, 105(30): 10553~10558
Zhao X, Gan L, Pan H, Kan D, Majeski M, Adam S A, Unterman T G. 2004. Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14-3-3-dependent and -independent mechanisms. Biochem J, 378, 839~849
Zheng H, You H, Zhou X Z, Murray S A, Uchida T, Wulf G, Gu L, Tang X, Lu K P, Xiao Z X. 2002. The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature, 419: 849~53
Zheng P Z, Wang K K, Zhang Q Y, Huang Q H, Du Y Z, Zhang Q H, Xiao D K, Shen S H, Imbeaud S, Eveno E, Zhao C J, Chen Y L, Fan H Y, Waxman S, Auffray C, Jin G, Chen S J. 2005. Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A, 102: 7653~7658
Zhou G, Zhang J, Wang Z, Chen S, Chen Z. 2007. Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy. Phil Trans R Soc B, 362: 959~971
Zubilewicz A, Hecquet C, Jeanny J C, Soubrane G, Courtois Y, Mascarelli F. 2001. Two distinct signalling pathways are involved in FGF2-stimulated proliferation of choriocapillary endothelial cells: a comparative study with VEGF. Oncogene, 20: 1403~1413
孙逸武. 1997.早幼粒细胞白血病诱导分化过程中维甲酸调控基因的研究. [博士学位论文].上海:上海第二医科大学
张囡囡. 2009.维甲酸诱导基因-I(Rig-I)对正常和白血病髓系造血的调控作用和相关分子机制研究. [博士学位论文].上海:中科院上海健康研究所
Actor B, Cobbers J M, Buschges R, Wolter M, Knobbe C B, Lichter P, Reifenberger G, Weber R G. 2002. Comprehensive analysis of genomic alterations in gliosarcoma and its two tissue components. Genes Chromosomes Cancer, 34: 416~427
Akira S, Uematsu S, Takeuchi O. 2006. Pathogen recognition and innate immunity. Cell, 124: 783~801
Alessi D R, Kozlowski M T, Weng Q P, Morrice N, Avruch J. 1998. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro. Curr Biol, 8: 69~81
Alff P J, Sen N, Gorbunova E, Gavrilovskaya I N, Mackow E R. 2008. The NY-1 hantavirus Gn cytoplasm ic tail coprecipitates TRAF3 and inhibits cellular interferon responses by disrupting TBK1–TRAF3 complex formation. J Virol, 82(18): 9115~9122
Ameres S L, Martinez J, Schroeder R. 2007. Molecular basis for target RNA recognition and cleavage by human RISC. Cell, 130: 101~112
Andrejeva J, Childs K S, Young D F, Carlos T S, Stock N, Goodbourn S, Randall R E. 2004. The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-b promoter. Proc Natl Acad Sci USA, 101(49): 17264~17269
Andrejeva J, Childs K S, Young D F, Carlos T S, Stock N, Goodbourn S. 2004. The V proteins of paramy xoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc Natl Acad Sci U S A, 101(49): 17264~17269
Aoki M, Blazek E, Vogt PK. 2001. A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt. Proc Natl Acad Sci U S A, 98: 136~141
Aoki M, Jiang H, Vogt P K. 2004. Proteasomal degradation of the FoxO1 transcriptional regulator in cells transformed by the P3k and Akt oncoproteins. Proc Natl Acad Sci USA, 101: 13613~13617
Arbiser J L, Kau T, Konar M, Narra K, Ramchandran R, Summers S A, Vlahos C J, Ye K, Perry B N, Matter W, Fischl A, Cook J, Silver P A, Bain J, Cohen P, Whitmire D, Furness S, Govindarajan B, Bowen J P. 2007. Solenopsin, the alkaloidal component of the fire ant (Solenopsis invicta), is a naturally occurring inhibitor of phosphatidylinositol-3-kinase signaling and angiogenesis. Blood, 109: 560~565
Arimoto K, Takahashi H, Hishiki T, Konishi H, Fujita T, Shimotohno K. 2007. Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proc Natl Acad Sci USA, 104: 7500~5
Avdulov S, Li S, Michalek V, Burrichter D, Peterson M, Perlman D M, Manivel J C, Sonenberg N, Yee D, Bitterman P B, Polunovsky V A. 2004. Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells. Cancer Cell, 5: 553~563
Avruch J, Belham C, Weng Q, Hara K, Yonezawa K. 2001. The p70 S6 kinase integrates nutrient and growth signals to control translational capacity. Prog Mol Subcell Biol, 26: 115~154
Bachman K E, Argani P, Samuels Y, Silliman N, Ptak J, Szabo S, Konishi H, Karakas B, Blair B G, Lin C, Peters B A, Velculescu V E, Park B H. 2004. The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther, 3: 772~775
Backers K, Blero D, Paternotte N, Zhang J, Erneux C. 2003. The termination of PI3K signalling by SHIP1 and SHIP2 inositol5-phosphatases. Adv Enzyme Regul, 43: 15~28
Backman S A, Ghazarian D, So K, Sanchez O, Wagner K U, Hennighausen L, Suzuki A, Tsao M S, Chapman W B, Stambolic V, Mak T W. 2004. Early onset of neoplasia in the prostate and skin of mice with tissuespecific deletion of Pten. Proc Natl Acad Sci U S A, 101: 1725~1730
Bakker W J, Blazquez-Domingo M, Kolbus A, Besooyen J, Steinlein P, Beug H, Coffer P J, Lowenberg B, Von Lindern M and Van Dijk TB. 2004. FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1. J Cell Biol, 164: 175~184
Balachandran S, Venkataraman T, Fisher P B, Barber G N. 2007. Fas-associated death domain-containing protein-mediated antiviral innate immune signaling involves the regulation of Irf7. J Immunol, 178(4): 2429~2439
Ballif B A, Roux P P, Gerber S A, MacKeigan J P, Blenis J, Gygi S P. 2005. Quantitative phosphorylation profiling of the ERK/p90 ribosomal S6 kinase-signaling cassette and its targets, the tuberous sclerosis tumor suppressors. Proc Natl Acad Sci USA, 102: 667~672
Bamming D, Horvath C M. 2009. Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I and LGP2. J Biol Chem, 284: 9700~12
Baron U, Freundlieb S, Gossen M, Bujard H. 1995. Co-regulation of two gene activities by tetracycline via a bidirectional promoter. Nucleic Acids Res, 23: 3605~3606
Barral P M, Morrison J M, Drahos J, Gupta P, Sarkar D, Fisher P B, Racaniello V R. 2007. MDA-5 is cleaved in poliovirus-infected cells. J Virol, 81: 3677~3684
Barral P M, Morrison J M, Drahos J, Gupta P, Sarkar D, Fisher P B, Racaniello V R. 2007. MDA-5 is cleaved in poliovirus-infected cells. J Virol, 81(8): 3677~3684
Barro M, Patton J T. 2007. Rotavirus NSP1 inhibits expression of type I interferon by antagonizing the function of interferon regulatory factors IRF3, IRF5, and IRF7. J Virol, 81(9): 4473~4481
Bauer S, Pigisch S, Hangel D, Kaufmann A, Hamm S. 2008. Recognition of nucleic acid and nucleic acid analogs by Toll-like receptors 7, 8 and 9. Immunobiology, 213: 315~28
Bauhofer O, Summerfield A, Sakoda Y, Tratschin J D, Hofmann M A, Ruggli N. 2007. Classical swine fever virus Npro interacts with interferon regulatory factor3 and induces its proteasomal degradation. J Virol, 81(7): 3087~3096
Bellacosa A, de Feo D, Godwin A K, Bell D W, Cheng J Q, Altomare D A, Wan M, Dubeau L, Scambia G, Masciullo V, Ferrandina G, Benedetti P P, Mancuso S, Neri G, Testa J R. 1995. Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int J Cancer 64: 280~285
Bellacosa A, Kumar C C, Di Cristofano A, Testa J R. 2005. Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res, 94:29~86
Benthin M, Dallmann I, Atzpodien J. 2001. 13cis- and all-transretinoic acid have antiproliferative effects on CML cells and render IFN alpha antiproliferative potency after combined treatment in vitro. Cancer Biother Radiopharm, 16: 323~331
Bernard J, Mathe G, Boulay J, Ceoard B, Chome J. 1959. Acute promyelocytic leukemia: a study made on 20 cases. Schweiz Med Wochenschr, 89: 604~608
Bernard J, Weil M, Boiron M. 1973. Acute promyelocytic leukemia: results of treatment by daunorubicin. Blood, 41: 489~496
Biggs W H, Meisenhelder J, Hunter T, Cavenee W K, Arden K C. 1999. Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci USA, 96: 7421~7426
Birck A, Ahrenkiel V, Zeuthen J, Hou-Jensen K, Guldberg P. 2000. Mutation and allelic loss of the PTEN/MMAC1 gene in primary and metastatic melanoma biopsies. J Invest Dermatol, 114: 277~280
Boone D L, Turer E E, Lee E G, Ahmad R C, Wheeler M T, Tsui C, Hurley P, Chien M, Chai S, Hitotsumatsu O, McNally E, Pickart C, Ma A. 2004. The ubiquitin-modifying enzyme A20 is required for termination of toll-like receptor responses. Nat Immunol, 5: 1052~60
Brazil D P, Yang Z Z, Hemmings B A. 2004. Advances in protein kinase B signalling: AKTion on multiple fronts. Trends Biochem Sci, 29: 233~242
Breitman T R, Collins S J, Keene B R. 1981. Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid. Blood, 57: 1000~1004
Breitman T R, Selonick S E, Collins S J. 1980. Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci U S A, 77: 2936~2940
Broderick D K, Di C, Parrett T J, Samuels Y R, Cummins J M, McLendon R E, Fults D W, Velculescu V E, Bigner D D, Yan H. 2004. Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas. Cancer Res, 64: 5048~5050
Brown D, Kogan S, Lagasse E, Brown D, Kogan S, Lagasse E, Weissman I, Alcalay M, Pelicci PG, Atwater S, Bishop JM. 1997. A PMLRARalpha transgene initiates murine acute promyelocytic leukemia. Proc Natl Acad Sci U S A, 94: 2551~2556
Brownawell A M, Kops G J, Macara I G, Burgering B M. 2001. Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular distribution and activity of the forkhead transcription factor AFX. Mol Cell Biol, 21: 3534~3546
Brunet A, Bonni A, Zigmond M J, Lin M Z, Juo P, Hu L S, Anderson M J, Arden K C, Blenis J and Greenberg ME. 1999. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell, 96: 857~868
Brunet A, Kanai F, Stehn J, Xu J, Sarbassova D, Frangioni J V, Dalal S N, DeCaprio J A, Greenberg M E, Yaffe M B. 2002.14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport. J Cell Biol, 156: 817~828
Burckstummer T, Baumann C, Blüml S, Dixit E, Dürnberger G, Jahn H, Planyavsky M, Bilban M, Colinge J, Bennett K L, Superti-Furga G. 2009. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol, 10(3): 266~272
Burgering B M, Coffer P J. 1995. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature, 376: 599~602
Byun D S, Cho K, Ryu B K, Lee M G, Park J I, Chae K S, Kim H J, Chi S G. 2003. Frequent monoallelic deletion of PTEN and its reciprocal association with PIK3CA amplification in gastric carcinoma. Int J Cancer, 104: 318~327
Campbell I G, Russell S E, Choong D Y, Montgomery K G, Ciavarella M L, Hooi C S, Cristiano B E, Pearson R B, Phillips W A. 2004. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res, 64: 7678~7681
Cantley L C, Neel B G. 1999. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A, 96: 4240~4245 Cantley L C. 2002. The phosphoinositide 3-kinase pathway, Science 296:1655~1657
Carmeliet P, Lampugnani M G, Moons L, Breviario F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oostuyse B, Dewerchin M, Zanetti A, Angellilo A, Mattot V, Nuyens D, Lutgens E, Clotman F, de Ruiter M C, Gittenberger-de Groot A, Poelmann R, Lupu F, Herbert J M, Collen D, Dejana E. 1999. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell, 98: 147~157
Cassady K A. 2005. Human cytomegalovirus TRS1 and IRS1 gene products block the double-stranded- RNA-activated host protein shut off response induced by herpes simplex virus type 1 infection. J Virol, 79(14): 8707~8715
Castaigne S, Chomienne C, Daniel M T, Ballerini P, Berger R, Fenaux P, Degos L. 1990. All trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia, I: clinical results. Blood, 76: 1704~1709
Castedo M, Ferri K F, Kroemer G. 2002. Mammalian target of rapamycin (mTOR): pro and anti-apoptotic. Cell Death Differ, 9: 99~100
Chan S, Scheulen M E, Johnston S, Mross K, Cardoso F, Dittrich C, Eiermann W, Hess D, Morant R, Semiglazov V, Borner M, Salzberg M, Ostapenko V, Illiger H J, Behringer D, Bardy-Bouxin N, Boni J, Kong S, Cincotta M, Moore L. 2005. Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol, 23: 5314~5322
Chang K, Elledge S J, Harmon G J. 2006. Lessons from nature: microRNA-based shRNA libraries. Nat Methods, 3(9):707~714
Chen W S, Xu P Z, Gottlob K, Chen M L, Sokol K, Shiyanova T. 2001. Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes Dev,15: 2203~2208
Chen Z X, Xue Y Q, Zhang R, Chen Z X, Xue Y Q, Zhang R, Tao R F, Xia X M, Li C, Wang W, Ling B J. 1991. A clinical and experimental study on all-trans retinoic acid treated acute promyelocytic leukemia patients.Blood, 78: 1413~1419
Chen Z, Brand NJ, Chen A, Chen Z, Brand N J, Chen A, Chen S J, Tong J H, Wang Z Y, Waxman S, Zelent A . 1993. Fusion between a novel Kruppel-like zinc finger gene and the retinoic acidreceptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J, 12: 1161~1167
Cheng G X, Zhu X H, Men X Q. 1999. Distinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF-RARalpha and NPM-RARalpha. Proc Natl Acad Sci U S A, 96: 6318~6323
Cheng J Q, Ruggeri B, Klein W M, Sonoda G, Altomare D A, Watson D K, Testa J R. 1996. Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci U S A, 93: 3636~3641
Child S J, Hakki M, De Niro, K L, Geballe A P. 2004. Evasion of cellular antiviral responses by human cytomegalovirus TRS1 and IRS1. J Virol, 78(1): 197~205
Childs K S, Andrejeva J, Randall R E, Goodbourn S. 2008. Mechanism of mda-5 inhibition by paramyxov irus V proteins. J Virol, 83(3): 1465~1473
Childs K, Stock N, Ross C, Andrejeva J, Hilton L, Skinner M. 2007. mda-5, but not RIG-I, is a common target for paramyxovirus V proteins. Virology, 359(1): 190~200
Chinnaiyan A M., O Rourke K, Tewari M, Dixit V M. 1995. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell, 81(4): 505~512
Choi K M, McMahon L P, Lawrence J C. 2003. Two motifs in the translational repressor PHAS-I required for efficient phosphorylation by mammalian target of rapamycin and for recognition by raptor. J Biol Chem, 278: 19667~19673
Chow S, Minden M D, Hedley DW. 2006. Constitutive phosphorylation of the S6 ribosomal protein via mTOR and ERK signaling in the peripheral blasts of acute leukemia patients. Exp Hematol, 34: 1183~1191
Corey S, Eguinoa A, Puyana-Theall K, Bolen J B, Cantley L, Mollinedo F, Jackson T R, Hawkins P T, Stephens L R. 1993. Granulocyte macrophage-colony stimulating factor stimulates both association and activation of phosphoinositide 3OH-kinase and src-related tyrosine kinase(s) in human myeloid derived cells. EMBO J, 12: 2681~2690
Cui S, Eisenacher K, Kirchhofer A, Brzozka K, Lammens A, Lammens K, Fujita T, Hopfner K P. 2008. The C-terminal regulatory domain is the RNA 5-triphosphate sensor of RIG-I. Mol Cell, 29: 169~79
Cui Y, Li M, Walton K D, Sun K, Hanover J A, Furth P A, Hennighausen L. 2001. The Stat3 ? 5 locus encodesnovel endoplasmic reticulum and helicase like proteins that are preferentially expressed in normal and neoplastic mammary tissue. Genomics, 78: 129~134
Cunningham I, Gee T S, Reich L M, Kempin S J, Naval A N, Clarkson BD. 1989. Acute promyelocytic leukemia: treatment results during a decade at Memorial Hospital. Blood, 73: 1116~1122
Daenen S, Vellenga E, Dobbenburgh O A, Halie M R. 1986. Retinoic acid as antileukemic therapy in a patient with acute promyelocytic leukemia and Aspergillus pneumonia. Blood, 67: 559~561
Datta S R, Dudek H, Tao X, Datta S R, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg M E. 1997. Akt phosphorylation of BAD couples survival signalsto the cell-intrinsic death machinery. Cell, 91: 231~241
de The′H, Chomienne C, Lanotte M, Degos L, Dejean A. 1990. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature, 347: 558~561
Degos L ,Chomienne C, Daniel M T, Berger R, Dombret H, Fenaux P. 1990. Treatment of first relapse in acute promyelocytic leukaemia with all-trans retinoic acid. Lancet, 336: 1440~1441
Devaraj S G, Wang N, Chen Z, Chen Z, Tseng M, Barretto N, Lin R, Peters C J, Tseng C T, Baker S C, Li K. 2007. Regulation of IRF-3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus. J Biol Chem, 282(44): 32208~32221
Dijkers P F, Medemadagger R H, LammersJ J, Koenderman L, Coffer P J. 2000b. Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1. Curr Biol, 10: 1201~1204
DiPerna G, Stack J, Bowie A G, Boyd A, Kotwal G, Zhang Z. 2004. Poxvirus protein N1L targets the I-kappaB kinase complex, inhibits signaling to NF-kappaB by the tumor necrosis factor superfamily of receptors, and inhibits NF-kappaB and IRF3 signaling by toll-like receptors. J Biol Chem, 279(35): 36570~36578
Drexler H G. 1996. Expression of the FLT-3 receptor and response to FLT3 ligand by leukemic cells. Leukemia, 10: 588~599
Duronio V, Scheid M P, Ettinger S. 1998. Downstream signalling events regulated by phosphatidylinositol 3-kinase activity. Cell Signal, 10: 233~239
Easton R M, Cho H, Roovers K, Shineman D W, Mizrahi M, Forman M S, Lee V M, Birnbaum M J. 2005. Role for Akt3/protein kinase Bg in attainment of normal brain size. Mol Cell Biol, 25: 1869~1878
Ermoian R P, Furniss C S, Lamborn K R, Basila D, Berger M S, Gottschalk A R, Nicholas M K, Stokoe D, Haas-Kogan D A. 2002. Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival. Clin Cancer Res, 8: 1100~1106
Fenaux P, Wang Z Z, Degos L. 2007. Treatment of acute promyelocytic leukemia by retinoids. Curr Top Microbiol Immunol, 313: 101~128
Fernandes-Alnemri T, Yu J W, Datta P, Wu J, Alnemri E S. 2009. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature, 458: 509~13
Fingar D C, Richardson C J, Tee A R, Cheatham L, Tsou C, Blenis J. 2004. mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E. Mol Cell Biol, 24: 200~216
Fingar D C, Salama S, Tsou C, Harlow E, Blenis J. 2002. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev, 16: 1472~1487
Fire A, Xu S, Montgomery M K, Kostas S A, Driver S E, Mello C C. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 391: 806~811
Fitzgerald K A, McWhirter S M, Faia K L, Rowe D C, Latz E, Golenbock D T, Coyle A J, Liao S M, Maniatis T. 2003. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol, 4: 491~496
Flynn P J, Miller W J, Weisdorf D J, Arthur D C, Brunning R, Branda R F. 1983. Retinoic acid treatment of acute promyelocytic leukemia: in vitro and in vivo observations. Blood, 62: 1211~1217 for virus-triggered IFN-beta signaling. Mol Cell, 19: 727~740
Franke T F, Hornik C P, Segev L, Shostak G A, Sugimoto C. 2003. PI3K/Akt and apoptosis: size matters. Oncogene, 22: 8983~8998
Frauwirth K A, Riley J L, Harris M H, Frauwirth K A, Riley J L, Harris M H. 2002. The CD28 signaling pathway regulates glucose metabolism. Immunity, 16: 769~777
Fredericksen B L, Keller B C, Fornek J, Katze M G, Gale M Jr. 2008. Establishment and maintenance of the innate antiviral response to West Nile Virus involves both RIG-I and MDA5 signaling through IPS-1. J Virol, 82(2): 609~616
Friedman C S, O’Donnell M, Legarda-Addison D, Ng A, Cardenas W B, Yount J S, Moran T M, Basler C F, Komuro A, Horvath C M, Xavier R, Ting A T. 2008. Tumor suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. EMBO, Reports 9(9): 930~6
Friend C, Scher W, Holland J G, Sato T. 1971. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A, 68: 378~382
Furnari F B, Huang H J, Cavenee W K. 1998. The phosphoinositol phosphatase activity of PTEN mediates a serum-sensitive G1 growth arrest in glioma cells. Cancer Res, 58: 5002~5008
Furnari F B, Lin H, Huang H-J S, Cavenee W K. 1997.Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain. Proc Natl Acad Sci U S A, 94: 12479~12484
Gack M U, Shin Y C, Joo C H, Urano T, Liang C, Sun L. 2007. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature, 446: 916~20
Galanis E, Buckner J C, Maurer M J, Kreisberg J I, Ballman K, Boni J, Peralba J M, Jenkins R B, Dakhil S R, Morton R F, Jaeckle K A, Scheithauer B W, Dancey J, Hidalgo M, Walsh D J. 2005. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J Clin Oncol, 23: 5294~5304
Gee P, Chua P K, Gevorkyan J, Klumpp K, Najera I, Swinney D C, Deval J. 2008. Essential role of the N-terminal domain in the regulation of RIG-I ATPase activity. J Biol Chem, 283(14): 9488～9496
Gilliet M, Cao W, Liu Y J. 2008. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol, 8: 594~606
Gingras A C, Gygi S P, Raught B, Polakiewicz R D, Abraham RT, Hoekstra M F. 1999a. Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism. Genes Dev 13: 1422~1437
Gingras A C, Raught B, Gygi S P, Niedzwiecka A, Miron M, Burley S K, Polakiewicz R D, Wyslouch-Cieszynska A, Aebersold R, Sonenberg N. 2001. Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev, 15: 2852~2864
Gingras A C, Raught B, Sonenberg N. 1999b. eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu Rev Biochem, 68: 913~963
Gold M R, Duronio V, Saxena S P, Schrader J W, Aebersold R. 1994. Multiple cytokines activate phosphatidylinositol 3-kinase in hemopoietic cells: Association of the enzyme with various tyrosine-phosphorylated proteins. J Biol Chem, 269: 5403~5412
Gossen M, Buard H. 1992. Tight control of gene expression in man malian cells by Tetracycline responsive promoters. Proc Natl Acad Sci USA, 89(12): 5547~5551
Granville C A, Memmott R M, Gills J J, Dennis P A. 2006. Handicapping the race to develop inhibitors of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway. Clin Cancer Res, 12: 679~689
Grolleau A, Bowman J, Pradet-Balade B, Puravs E, Hanash S, Garcia-Sanz JA. 2002. Global and specific translational control by rapamycin in T cells uncovered by microarrays and proteomics. J Biol Chem 277: 22175~22184
Guo B, Cheng G. 2007. Modulation of the interferon antiviral response by the TBK1 ? IKKi adaptor protein TANK. J Biol Chem, 282: 11817~11826
Haasnoot J, de Vries W, Geutjes E J, Prins M, de Haan P, Berkhout B. 2007. The Ebola virus VP35 protein is a suppressor of RNA silencing. PLoS Pathog, 3: 794~803
Habjan M, Andersson I, Klingstrom J, Schumann M, Martin A, Zimmermann P, Wagner V, Pichlmair A, Schneider. 2008. Processing of genome 5′termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction. PLoS ONE, 3(4): 2032
Hacker H, Redecke V, Blagoev B, Kratchmarova I, Hsu L C, Wang G G, Kamps M P, Raz E, Wagner H, Hacker G, Mann M, Karin M. 2006. Specificity in toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature, 439: 204~7
Hahn-Windgassen A, Nogueira V, Chen C C, Skeen J E, Sonenberg N, Hay N. 2005. Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity. J Biol Chem, 280: 32081~32089
Hakki M, Geballe A P. 2005. Double-stranded RNA binding by human cytomegalovirus pTRS1. J Virol, 79(12): 7311~7318
Hanada M, Feng J, Hemmings B A. 2004. Structure, regulation and function of PKB/AKT– a major therapeutic target. Biochim Biophys Acta, 1697: 3~16
Harima Y, Sawada S, Nagata K, Sougawa M, Ostapenko V, Ohnishi T. 2001. Harris T E, Chi A, Shabanowitz J, Hunt D F, Rhoads R E, Lawrence Jr JC. 2006. mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin. EMBO J 25: 1659~1668
Hartmann C, Bartels G, Gehlhaar C, Holtkamp N, von Deimling A. 2005. PIK3CA mutations in glioblastoma multiforme. Acta Neuropathol, 109639~642
Haslam R J, Koide H B, Hemmings B A. 1993. Pleckstrin domain homology. Nature, 363: 309~310
Hay N, Sonenberg N. 2004. Upstream and downstream of mTOR. Genes Dev, 18: 1926~1945
He L-Z, Guidez F, Tribioli C, Peruzzi D, Ruthardt M, Zelent A, Pandolfi PP. 1998. Distinct interactions of PML-RARalpha and PLZF-RARalpha with co-repressors determine differential responses to RA in APL. Nat Genet, 18: 126~135
Hemmi H, Takeuchi O, Sato S, Yamamoto M, Kaisho T, Sanjo H, Kawai T, Hoshino K, Takeda K, Akira S. 2004. The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection. J Exp Med, 199: 1641~1650
Hennessy B T, Smith D L, Ram P T, Lu Y, Mills G B. 2005. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 4: 988~1004
Herbert T P, Fahraeus R, Prescott A, Lane D P, Proud C G. 2000. Rapid induction of apoptosis mediated by peptides that bind initiation factor eIF4E. Curr Biol, 10: 793~796
Hillestad LK. 1957. Acute promyelocytic leukemia. Acta Med Scand, 159:189~194
Holz M K, Ballif B A, Gygi S P, Blenis J. 2005. mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell, 123:569~580
Honda K, Takaoka A, Taniguchi T. 2006. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity, 25: 349~360
Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N, Taniguchi T. 2005. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature, 434: 772~777
Horman S, Vertommen D, Heath R, Neumann D, Mouton V, Woods A, Schlattner U, Wallimann T, Carling D, Hue L, Rider M H. 2006. Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinaseα-subunits in heart via hierarchical phosphorylation of Ser485/491. J Biol Chem, 281: 5335~5340
Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, Caffrey D R, Latz E, Fitzgerald K A. 2009. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature, 458: 514~8
Hornung V, Ellegast J, Kim S, Brzózka K, Jung A, Kato H, Poeck H, Akira S, Conzelmann K K, Schlee M, Endres S. 2006. 5’-Triphosphate RNA is the ligand for RIG-I. Science, 314: 994~997
Hresko R C, Mueckler M. 2005. mTOR/RICTOR is the Ser473 kinase for Akt/PKB in 3T3-L1 adipocytes. J Biol Chem, 280: 40406~40416
Hsu H, Huang J, Shu H B, Baichwal V, Goeddel D V. 1996. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity, 4(4): 387~396
Hu M C, Lee D F, Xia W, Golfman L S, Ou-Yang F, Yang J Y, Zou Y, Bao S, Hanada N, Saso H, Kobayashi R and Hung M C. 2004. IκB Kinase Promotes Tumorigenesis through Inhibition of Forkhead FOXO3a. Cell, 117: 225~237
Huang F, Adelman J, Jiang H, Goldstein N I, Fisher P B. 1999a. Identification and temporal expression pattern of genes modulated during irreversible growth arrest and terminal differentiation in human Huang F, Adelman J, Jiang H, Goldstein N I, Fisher P B. 1999b. Differentiation induction subtraction hybridization (DISH): an approach for cloning genes differentially expressed during growth arrest and Huang H, Regan K M, Wang F, Wang D, Smith D I, van Deursen J M, Tindall D J.. 2005. Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proc Natl Acad Sci USA, 102: 1649~1654
Huang J, Liu T, Xu LG, Chen D, Zhai Z, Shu H B. 2005. SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways. EMBO J, 24: 4018~28
Huang M E, Ye Y C, Chen S R, Chai J R, Lu J X, Zhoa L, Gu L J, Wang Z Y. 1988. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood, 72(2): 567~572
Huang M E, Ye Y C, Chen S R, Zhao J C, Gu L J, Cai J R, Zhao L, Xie J X, Wang Z Y. 1987. All-trans retinoic acid with or without low dose cytosine arabinoside in acute promyelocytic leukemia: report of 6 cases. Chin Med J. (Engl), 100: 949~953
Hutvágner G, Zamore P D. 2002. RNAi: nature abhors a double-strand. Curr Opin Genet Dev, 12: 225~232
Ihle N T, Paine-Murrieta G, Berggren M I, Baker A, Tate W R, Wipf P, Abraham R T, Kirkpatrick D L, Powis G. 2005. The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts. Mol Cancer Ther, 4: 1349~1357
Ikenoue T, Kanai F, Hikiba Y, Obata T, Tanaka Y, Imamura J, Ohta M, Jazag A, Guleng B, Tateishi K, Asaoka Y, Matsumura M, Kawabe T, Omata M. 2005. Functional analysis of PIK3CA gene mutations in human colorectal cancer. Cancer Res, 65: 4562~4567
Inoki K, Zhu T, Guan K L. 2003. TSC2 mediates cellular energy response to control cell growth and survival. Cell, 115: 577~590
Ishii K J, Coban C, Kato H, Takahashi K, Torii Y, Takeshita F. 2006. A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA. Nat Immunol, 7: 40~8
Ishii Ken J, Kawagoe Tatsukata, Koyama Shohei, Matsui Kosuke, Kumar Himanshu, Kawai Taro, Uematsu Satoshi, Takeuchi Osamu, Takeshita Fumihiko, Coban Cevayir, Akira Shizuo. 2008. TANK-binding kinase-1delineates innate and adaptive immune responses to DNA vaccines. Nature, 451: 725~729
Ishikawa H, Barber G N. 2008. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature, 455: 674~678
Janeway C A Jr, Medzhitov R. 2002. Innate immune recognition. Annu Rev Immunol, 20: 197~216
Jiang B H, Zheng J Z, Aoki M, Vogt P K. 2000. Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Proc Natl Acad Sci U S A, 97: 1749~1753
Joo C H, Shin Y C, Gack M, Wu L, Levy D, Jung J U. 2007. Inhibition of interferon regulatory factor 7 (IRF7)-mediated interferon signal transduction by the Kaposi's sarcoma-associated herpesvirus viral IRF homolog vIRF3. J Virol, 81(15): 8282~8292
Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, Xin K Q, Ishii K J, Kawai T, Akira S, Suzuki K, Okuda K. 2007. The Atg5-Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci USA, 104: 14050~5
Kakizuka A, Miller W H, Umesono K ,Warrell RP, Frankel S R, Murty V V, Dmitrovsky E, Evans RM. 1991. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell, 66: 663~674
Kang D C, Gopalkrishnan R V, Lin L, Randolph A, Valerie K, Pestka S, Fisher P B. 2004. Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon responsive apoptosis-inducing gene. Oncogene, 23: 1789~800
Kang D C, Gopalkrishnan R V, Wu Q, Jankowsky E, Pyle A M, Fisher P B. 2002. mda-5: An interferon -inducible putative RNA helicase with double-stranded RNA dependent ATPase activity and melanoma growth-suppressive properties. Proc Natl Acad Sci USA, 99: 637~642
Kang S, Bader A G, Vogt P K. 2005. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci USA, 102: 802~807
Kaplan D R, Whitman M, Schaffhausen B, Pallas D C, White M, Cantley L, Roberts T M. 1987. Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity. Cell, 50: 1021~1029
Kato H, Sato S, Yoneyama M, Yamamoto M, Uematsu S, Matsui K, Tsujimura T, Takeda K, Fujita T, Takeuchi O, Akira S. 2005. Cell type-specific involvement of RIG-I in antiviral response. Immunity, 23(1): 19~28
Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K. 2006. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature, 441: 101~5
Kawai T, Akira S. 2008. Toll-like receptor and RIG-I-like receptor signaling. Ann N Y Acad Sci, 1143: 1~20
Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii K J, Takeuchi O, Akira S. 2005. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol, 6(10): 981~988
Kayagaki N, Phung Q, Chan S, Chaudhari R, Quan C, O’Rourke K M, Eby M, Pietras E, Cheng G, Bazan J F, Zhang Z, Arnott D, Dixit V M. 2007. DUBA: a deubiquitinase that regulates type I interferon production. Science, 318: 1628~32
Khwaja A, Lehmann K, Marte B M, Downward J. 1998. Phosphoinositide 3-kinase induces scattering and tubulogenesis in epithelial cells through a novel pathway. J Biol Chem, 273: 18793~18801
Knobbe C B, Reifenberger G. 2003. Genetic alterations and aberrant expression of genes related to the phosphatidyl-inositol-3′-kinase/protein kinase B(Akt) signal transduction pathway in glioblastomas. Brain Pathol, 13: 507~518
Kohno T, Takahashi M, Manda R, Yokota J. 1998. Inactivation of the PTEN/MMAC1/TEP1 gene in human lung cancers. Genes Chromosomes Cancer, 22: 152~156
Komuro A, Horvath C M. 2006. RNA- and virusindependent inhibition of antiviral signaling by RNA helicase LGP2. J Virol, 80: 12332~12342
Kops G J, de Ruiter N D, De Vries-Smits A M, Powell D R, Bos J L, Burgering B M. 1999. Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature, 398:630~634
Kornblau S M, Womble M, Qiu Y H, Jackson C E, Chen W, Konopleva M. 2006. Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia. Blood, 108: 2358~2365
Kovacsovics M, Martinon F, Micheau O, Bodmer J L, Hofmann K, Tschopp J. 2002. Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation. Curr Biol, 12(10): 838~843
Krieg A M. 2007. The toll of too much TLR7. Immunity, 27: 695~7
Laleh Shayesteh, Yiling Lu, Wen-Lin Kuo, Russell Baldocchi, Tony Godfrey, Colin Collins, Daniel Pinkel, Bethan Powell, Gordon B Mills, Joe W Gray. 1999. PIK3CA is implicated as an oncogene in ovarian cancer. Nature Genet, 21: 99~102
Lam P K, To E W, Chan E S, Liew C T, Lung I W, King W K. 2001. In vitro inhibition of head and neck cancer-cell growth by human recombinant interferon-alpha and 13-cis-retionic acid. Br J Biomed Sci, 58: 226~229
Lee E G, Boone D L, Chai S, Libby S L, Chien M, Lodolce J P, Ma A. Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science 2000, 289: 2350~4
Lee J W, Soung Y H, Kim S Y, Lee H W, Park W S, Nam S W, Kim S H, Lee J Y, Yoo N J, Lee S H. 2005. PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene, 24: 1477~1480
Lee S, Comer F I, Sasaki A, McLeod I X, Duong Y, Okumura K, Yates J R 3rd, Parent C A, Firtel R A. 2005. TOR complex 2 integrates cell movement during chemotaxis and signal relay in Dictyostelium. Mol Biol Cell, 16: 4572~4583
LeeY, Kim M, Han J. 2004. MicroRNA genes are transcribed by RNA polymerase II. EMBO J, 23(20): 4051~4060
Lefort S, Soucy-Faulkner A, Grandvaux N, Flamand L. 2007. Binding of Kaposi's sarcoma-associated herpesvirus K-bZIP to interferon-responsive factor 3 elements modulates antiviral gene expression. J Virol 81(20): 10950~10960
Levine D A, Bogomolniy F, Yee C J, Lash A, Barakat R R, Borgen P I, Boyd J. 2005. Frequent mutation of the PIK3CA gene in ovarian and breast cancers. Clin Cancer Res, 11: 2875~2878
Li G, Robinson G W, Lesche R, Martinez-Diaz H, Jiang Z, Rozengurt N, Wagner K U, Wu D C, Lane T F, Liu X, Hennighausen L,Wu H. 2002. Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development, 129: 4159~4170
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang S I, Puc J, McCombie. 1997. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 275: 1943~1947
Li V S, Wong C W, Chan T L, Chan A S, Zhao W, Chu K M, So S, Chen X, Yuen S T, Leung S Y. 2005 .Mutations of PIK3CA in gastric adenocarcinoma. BMC Cancer, 5: 29
Li X D, Sun L, Seth R B, Pineda G, Chen Z J. 2005. Hepatitis C virus protease NS3 ? 4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci USA, 102: 17717~17722
Liaw D, Marsh D J, Li J, Dahia P L, Wang S I, Zheng Z, Bose S, Peacocke M .1997. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet, 16: 64~67
Lin R, Genin P, Mamane Y, Sgarbanti M, Battistini A, Harrington W J. 2001. HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators. Oncogene, 20(7): 800~811
Lin R, Lacoste J, Nakhaei P, Sun Q, Yang L, Paz S, Wilkinson P, Julkunen I, Vitour D, Meurs E, Hiscott J. 2006. Dissociation of a MAVS/IPS-1/VISA/Cardif-IKKepsilon molecular complex from the mitochondrial outer membrane by hepatitis C virus NS3-4A proteolytic cleavage. J Virol, 80(12): 6072~6083
Lin R, Yang L, Nakhaei P, Sun Q, Sharif-Askari E, Julkunen I, Hiscott J. 2006. Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. J Biol Chem, 281: 2095~103
Lindner D J, Borden E C, Kalvakolanu D V. 1997. Synergistic antitumor effects of a combination of interferons and retinoic acid on human tumor cells in vitro and in vivo. Clin Cancer Res, 3: 931~937
Lingen M W, Polverini P J, Bouck N P. 1998. Retinoic acid and interferon alpha act synergistically as antiangiogenic and antitumor agents against human head and neck squamous cell carcinoma. Cancer Res, 58: 5551~5558
Lippman, S M, Parkinson D R, Itri L M, Weber R S, Schantz S P, Ota D M, Schusterman M A, Krakoff I H, Gutterman J U, Hong W K. 1992. 13-cis-Retinoic acid and interferon alpha-2a: effective combination therapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst, 84: 235~241
Liu T X, Zhang J W, Tao J, Zhang R B, Zhang Q H, Zhao C J, Tong J H, Lanotte M, Waxman S, Chen S J, Mao M, Hu G X, Zhu L, Chen Z. 2000. Gene expression networks underlying retinoic acid-induced differentiation of acute promyelocytic leukemia cells. Blood, 96(4): 1496~1504
Liu Y C, Penninger J, Karin M. 2005. Immunity by ubiquitylation: a reversible process of modification. Nat Rev Immunol, 5(12): 941~952
Lo-Coco F, Ammatuna E. 2006. The biology of acute promyelocytic leukemia and its impact on diagnosis and treatment. Hematol (Am Soc Hematol Educ Program), 156~161
Loo Y M, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, Akira S, Gill M A, García -Sastre A, Katze M G, Gale M Jr. 2008. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol, 82(1): 335~345
Lu L L, Puri M, Horvath C M, Sen G C. 2008. Select paramyxoviral V proteins inhibit IRF3 activation by acting as alternative substrates for inhibitor of kappaB kinase epsilon (IKKe)/TBK1. J Biol Chem, 283(21): 14269~14276
Lynch M, Fitzgerald C, Johnston K A, Wang S, Schmidt E V. 2004. Activated eIF4E-binding protein slows G1 progression and blocks transformation by c-myc without inhibiting cell growth. J Biol Chem, 279: 3327~3339
Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi P P. 2005. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell, 121: 179~193
Maehama T, Dixon J E. 1998. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem, 273: 13375~13378
Mamane Y, Petroulakis E, LeBacquer O, Sonenberg N. 2006. MTOR, translation initiation and cancer. Oncogene, 25:6416~22
Marsh D J, Coulon V, Lunetta K L, Marsh D J, Coulon V, Lunetta K L, Rocca-Serra P, Dahia P L M, Zheng Z, Liaw D. 1998. Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet, 7: 507~515
Martinon F, Tschopp J. 2007. Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ, 14: 10~22
Massad L S, Turyk M E, Bitterman P, Wilbanks G D. 1996. Interferon-alpha and all-trans-retinoic acid reversibly inhibit the in vitro proliferation of cell lines derived from cervical cancers. Gynecol Oncol, 60: 428~434
Matsuzaki H, Daitoku H, Hatta M, Tanaka K, Fukamizu A. 2003. Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation. Proc Natl Acad Sci USA, 100: 11285~11290
McManus E J, Collins B J, Ashby P R, Prescott A R, Murray-Tait V, Armit L J, Arthur J S, Alessi D R. 2004. The in vivo role of PtdIns(3,4,5)P3 binding to PDK1 PH domain defined by knockin mutation. EMBO J, 23: 2071~2082
McWhirter S M, Fitzgerald K A, Rosains J, Rowe D C, Golenbock D T, Maniatis T. 2004. IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts. Proc Natl Acad Sci USA, 101: 233~8
Medema R H, Kops G J, Bos J L, Burgering B M. 2000. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 404: 782~787
Medzhitov R. 2001. Toll-like receptors and innate immunity. Nature Rev Immunol, 1(2): 135~145
Meijer A J, Codogno P. 2004. Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol, 36:2445~62
Melroe G T, Silva L, Schaffer P A, Knipe D M. 2007. Recruitment of activated IRF-3 and CBP/p300 to herpes simplex virus ICPO nuclear foci: potential role in blocking IFN-beta induction. Virology 360(2): 305~321
Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J. 2005. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature, 437: 1167~72
Michallet M C, Meylan E, Ermolaeva M A, Vazquez J, Rebsamen M, Curran J, Poeck H, Bscheider M, Hartmann G, K?nig M, Kalinke U, Pasparakis M, Tschopp J. 2008. TRADD protein is an essential component of the RIG-like helicase antiviral pathway. Immunity, 28: 651~661
Micheau O, Tschopp J. 2003. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell, 114: 181~190
Min Y H, Eom J I, Cheong J W, Maeng H O, Kim J Y, Jeung H K. 2003. Constitutive phosphorylation of Akt/PKB protein in acute myeloid leukemia: its significance as a prognostic variable. Leukemia, 17: 995~997
Modur V, Nagarajan R, Evers B M, Milbrandt J. 2002. FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. J Biol Chem, 277: 47928~47937
Moore C B, Bergstralh D T, Duncan J A, Lei Y, Morrison T E, Zimmermann A G, Heise M T, Chen Z, Ting J P. 2008. NLRX1 is a regulator of mitochondrial antiviral immunity. Nature, 451: 573~7
Mothe-Satney I, Yang D, Fadden P, Haystead T A J, Lawrence J C. 2000b. Multiple mechanisms control phosphorylation of PHAS-I in five (S/T)P sites that govern translational repression. Mol Cell Biol, 20: 3558~3567
Musto P, Sajeva M R, Sanpaolo G, D’Arena G, Scalzulli P R, Carotenuto M. 1997. All-trans-retinoic acid in combination with alpha-interferon and dexamethasone for advanced multiple myeloma. Haematologica, 82: 354~356
Mutation of the PTEN gene in advanced cervical cancer correlated with tumor progression and poor outcome after radiotherapy. Int J Oncol, 18: 493~497
Myers M P, Pass I, Batty I H, Van der Kaay J, Stolarov J P, Hemmings B A, Wigler M H, Downes C P, Tonks N K. 1998. The lipid phosphatase activity of PTEN is critical for its tumor supressor function. Proc Natl Acad Sci U S A, 10; 95(23): 13513~13518
Myers M P, Stolarov J P, Eng C, Li J, Wang S I, Wigler M H, Parsons R, Tonks N K. 1997. P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc Natl Acad Sci U S A, 94: 9052~9057
Nakatani K, Thompson D A, Barthel A, Sakaue H, Liu W, Weigel R J, Roth R A. 1999. Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines. J Biol Chem, 274: 21528~21532
Nakayama K, Nakayama N, Kurman R J, Cope L, Pohl G, Samuels Y, Velculescu V E, Wang T L, Shih I. 2006. Sequence mutations and amplification of PIK3CA and AKT2 genes in purified ovarian serous neoplasms. Cancer Biol Ther, 5: 779~785
Nervi C, Ferrara F F, Fanelli M, Rippo M R, Tomassini B, Ferrucci P F, Ruthardt M. 1998. Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein. Blood, 92: 2244~2251
Neznanov N, Chumakov K M, Neznanova L, Almasan A, Banerjee A K., Gudkov A V. 2005. Proteolytic cleavage of the p65-RelA subunit of NF-kappaB during poliovirus infection. J Biol Chem, 280(25): 24153~24158
Ngo V N, Davis R E, Lamy L. 2006. A loss-of-function RNA interference screen for molecular targets in cancer. Nature, 41: 106~110
Nilsson B. 1984. Probable in vivo induction of differentiation by retinoic acid of promyelocytes in acute promyelocytic leukaemia. Br J Haematol, 57:365~371
NLRX1 is a mitochondrial NOD-like receptor that amplifies NF-kappaB and JNK pathways by inducing reactive oxygen species production. EMBO Rep, 9: 293~300
Nojima H, Tokunaga C, Eguchi S, Oshiro N, Hidayat S, Yoshino K, Hara K, Tanaka N, Avruch J, Yonezawa K. 2003. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem, 278: 15461~15464
O’Neill L A. 2008. The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol Rev, 226: 10~8
Obsil T, Ghirlando R, Anderson D E, Hickman A B, Dyda F. 2003. Two 14-3-3 binding motifs are required for stable association of Forkhead transcription factor FOXO4 with 14-3-3 proteins and inhibition of DNA binding. Biochemistry, 42: 15264~15272
Oganesyan G, Saha S K, Guo B, He J Q, Shahangian A, Zarnegar B, Perry A, Cheng G. 2006. Critical role of TRAF3 in the toll-like receptor-dependent and -independent antiviral response. Nature, 439: 208~11
Ogura Y, Inohara N, Benito A, Chen F F, Yamaoka S, Nunez G. 2001. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kB. J Biol Chem, 276(7): 4812~4818
Oh J S, Kucab J E, Bushel P R, Martin K, Bennett L, Collins J, DiAugustine R P, Barrett J C, Afshari C A, Dunn S E. 2002. Insulin-like growth factor-1 inscribes a gene expression profile for angiogenic factors and cancer progression in breast epithelial cells. Neoplasia, 4: 204~217
Okumura A, Alce T, Lubyova B, Ezelle H, Strebel K, Pitha P M. 2008. HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation. Virology, 373(1): 85~97
Opipari A W J, Boguski M S, Dixit V M. 1990. The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. J Biol Chem, 265: 14705~8
Otsuka M, Kato N, Moriyama M, Taniguchi H, Wang Y, Dharel N, Kawabe T, Omata M. 2005.Interaction between the HCV NS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses. Hepatology 41(5): 1004~1012
Papapetropoulos A, Fulton D, Mahboubi K., Kalb R G, O'Connor D S, Li F, Altieri D C, Sessa W C. 2000. Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway. J Biol Chem, 275: 9102~9105
Pedrero J M, Carracedo D G, Pinto C M, Zapatero A H, Rodrigo J P, Nieto C S, Gonzalez M V. 2005. Frequent genetic and biochemical alterations of the PI3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma. Int J Cancer, 114: 242~248
Perrot V, Rechler M M. 2005. The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. Mol Endocrinol, 19: 2283~2298
Perry A K, Chow E K, Goodnough J B, Yeh W C, Cheng G. 2004. Differential requirement for TANK -binding kinase-1 in type I interferon responses to toll-like receptor activation and viral infection. J Exp Med, 199: 1651~1658
Peso del L, Gonzalez-Garcia M, Page C, del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez. 1997. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science, 278: 687~689
Peterson TR, Sabatini D M. 2005. eIF3: a connecTOR of S6K1 to the translation preinitiation complex. Mol Cell, 20: 655~657
Pichlmair A, Schulz O, Tan C P, Naslund T I, Liljestrom P, Weber F, Reis e Sousa C. 2006. RIG-I mediated antiviral responses to single-stranded RNA bearing 5’-phosphates. Science, 314: 997~1001
Pierce G B Jr, Verney E L. 1961. An in vitro and in vivo study of differentiation in teratocarcinoma. Cancer, 14: 1017~1029
Pippig D A, Hellmuth J C, Cui S, Kirchhofer A, Lammens K, Lammens A, Schmidt A, Rothenfusser S, Hopfner, K P. 2009. Theregulatory domain of the RIG-I family ATPase LGP2 senses double-stranded Plas D R, Thompson C B. 2003. Akt activation promotes degradation of tuberin and FOXO3a via the proteasome. J Biol Chem, 278: 12361~12366
Plotch S J, Bouloy M, Ulmanen I. Krug R M. 1981. A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell, 23(3): 847~858
Plumet S, Herschke F, Bourhis J M, Valentin H, Longhi S, Gerlier D. 2007. Cytosolic 5’-triphosphate ended viral leader transcript of measles virus as activator of the RIG I-mediated interferon response. PLoS ONE, 2: 279
Polunovsky V A, Gingras A C, Sonenberg N, Peterson M, Tan A, Rubins J B, Manivel J C, Bitterman P B. 2000. Translational control of the antiapoptotic function of Ras. J Biol Chem, 275: 24776~24780
Potter J A, Randall R E, Taylor G L. 2008. Crystal structure of human IPS-1 ? MAVS ? VISA ? Cardif caspase activation recruitment domain. BMC Struct Biol, 8: 11
Proud C G. 2005. The eukaryotic initiation factor 4E-binding proteins and apoptosis. Cell Death Differ, 12: 541~546
Pullen N, Dennis P B, Andjelkovic M, Dufner A, Kozma S C, Hemmings B A, Thomas G. 1998. Phosphorylation and activation of p70s6k by PDK1. Science, 279: 707~710
Raffioni S, Bradshaw RA. 1992. Activation of phosphatidylinositol 3-kinase by epidermal growth factor, basic fibroblast growth factor, and nerve growth factor in PC12 pheochromocytoma cells. Proc Natl Acad Sci U S A, 89: 9121~9125
Ramaswamy S, Nakamura N, Sansal I, Bergeron L, Sellers W R. 2002. A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR. Cancer Cell, 2: 81~91
Rao P, Mufson R A. 1995. A membrane proximal domain of the human interleukin-3 receptor beta c subunit that signals DNA synthesis in NIH 3T3 cells 1995 specifically binds a complex of Src and Janus family tyrosine kinases and phosphatidylinositol 3-kinase. J Biol Chem, 270: 6886~6893
Rebsamen M, Meylan E, Curran J, Tschopp J. 2008. The antiviral adaptor proteins Cardif and Trif are processed and inactivated by caspases. Cell Death Differ, 15(11): 1804~1811
Redner RL. 2002. Variations on a theme: the alternate translocations in APL. Leukemia, 16: 1927~1932
Rena G., Prescott A R, Guo S, Cohen P, Unterman T G. 2001. Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in regulating 14-3-3 binding, transactivation and nuclear targetting. Biochem J, 354: 605~612
Ribeiro R C, Rego E. 2006. Management of APL in developing countries: epidemiology, challenges and opportunities for international collaboration. Hematol (Am Soc Hematol Educ Program), 162~168 RNA. Nucleic Acids Res, 37: 2014~25
Roberts T L, Idris A, Dunn J A, Kelly G M, Burnton C M, Hodgson S, Hardy L L, Garceau V, Sweet M J, Ross I L, Hume D A, Stacey K J. 2009. HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science, 323: 1057~60
Rothenfusser S, Goutagny N, DiPerna G, Gong M, Monks B G, Schoenemeyer A, Yamamoto M, Akira S, Fitzgerald K A. 2005. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. J Immunol, 175:5260~5268
Rowley J D, Golomb H M, Dougherty C. 1977. 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia. Lancet, 1: 549~550
Ruderman N B, Kapeller R, White M F, Cantley L C. 1990. Activation of phosphatidylinositol 3-kinase by insulin. Proc Natl Acad Sci U S A, 87: 1411~1415
Runde V, Aul C, Sudhoff T, Heyll A, Schneider W. 1992. Retinoic acid in the treatment of acute promyelocytic leukemia: inefficacy of the 13-cis isomer and induction of complete remission by the all-trans isomer complicated by thromboembolic events. Ann Hematol, 64: 270~272
Ryzhakov G, Randow F. 2007. SINTBAD, a novel component of innate antiviral immunity, shares a TBK1 -binding domain with NAP1 and TANK. EMBO J, 26: 3180~3190
Saal L H, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu J S, Malmstr?m P O, Mansukhani M, Enoksson J, Hibshoosh H, Borg A, Parsons R. 2005. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res,65: 2554~2559
Sachs L. 1978. Control of normal cell differentiation and the phenotypic reversion of malignancy in myeloid leukaemia. Nature, 274: 535~539
Saha S K, Pietras E M, He J Q, Kang J R, Liu S Y, Oganesyan G, Shahangian A, Zarnegar B, Shiba T L, and Cheng G. 2006. Regulation of antiviral responses by a direct and specific interaction between TRAF3 and cardif. EMBO J, 25: 3257~63
Saira K, Zhou Y, Jones C. 2007. The infected cell protein O encoded by bovine herpesvirus 1 (bICPO) induces degradation of interferon response factor 3 and consequently, inhibits beta interferon promoter activity. J Virol, 81(7): 3077~3086
Saito T, Hirai R, Loo Y M, Owen D, Johnson C L, Sinha S C, Akira S, Fujita T, Gale M Jr. 2007. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci USA, 104: 582~587
Saitoh T, Tun-Kyi A, Ryo A, Yamamoto M, Finn G, Fujita T, Akira S, Yamamoto N, Lu K P, Yamaoka S. 2006. Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1. Nat Immunol, 7: 598~605
Saitoh T, Yamamoto M, Miyagishi M, Taira K, Nakanishi M, Fujita T, Akira S, Yamamoto N, Yamaoka S. 2005. A20 is a negative regulator of IFN regulatory factor 3 signaling. J Immunol, 174: 1507~12
Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell S M, Riggins G J, Willson J K, Markowitz S, Kinzler K W, Vogelstein B, Velculescu VE. 2004. High frequency of mutations of the PIK3CA gene in human cancers. Science, 304: 554
Sansal I, Sellers W R. 2004. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol, 22: 2954~2963
Sanz M A, Jarque I, Martín G, Lorenzo I, Martínez J, Rafecas J, Pastor E, Sayas M J, Sanz G, Gomis F. 1988. Acute promyelocytic leukemia: therapy results and prognostic factors. Cancer, 61: 7~13
Sarbassov D D, Ali S M, Kim D H, Guertin D A, Latek R R, Erdjument-Bromage H, Tempst P, Sabatini D M. 2004. Rictor, a novel binding partner of mTOR, defines a rapamycininsensitiveand raptor-independent pathway that regulates the cytoskeleton. Curr Biol, 14: 1296~1302
Sarbassov D D, Guertin D A, Ali S M, Sabatini D M. 2005. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science, 307: 1098~1101
Sasai M, Shingai M, Funami K, Yoneyama M, Fujita T, Matsumoto M, Seya T. 2006. NAK-associated protein 1 participates in both the TLR3 and the cytoplasmic pathways in type I IFN induction. J Immunol, 177: 8676~8683
Schalm S S, Blenis J. 2002. Identification of a conserved motif required for mTOR signaling. Curr Biol, 12: 632~639
Schalm S S, Fingar D C, Sabatini D M, Blenis J. 2003. TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr Biol, 13:797~806
Schmidt M, Fernandez de Mattos S, van der Horst A, Klompmaker R, Kops G J, Lam E W, Burgering B M, Medema R H. 2002. Cell cycle inhibition by FoxO forkhead
Schroder M, Baran M, Bowie A G. 2008. Viral targeting ofDEADbox protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J, 27(15): 2147~2157
Schubert D, Humphreys S, Jacob F, de Vitry F. 1971. Induced differentiation of a neuroblastoma. Dev Biol, 25: 514~546
Schulze-Bergkamen H, Fleischer B, Schuchmarm M. 2006. Suppression of Mcl-l via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction. BMC Cancer, 6(10):232
Seoane J, Le H V, Shen L, Anderson S A, Massague, J. 2004. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell, 117: 211~223
Seth R B, Sun L, Ea C K, Chen Z J. 2005. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell, 122: 669~682
Shahbazian D, Roux P P, Mieulet V, Cohen M S, Raught B, Taunton J. 2006. The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity. EMBO J, 25: 2781~2791
Sharma S, tenOever B R, Grandvaux N, Zhou G P, Lin R, Hiscott J. 2003. Triggering the interferon antiviral response through an IKK-related pathway. Science, 300: 1148~51
Shaw R J, Bardeesy N, Manning B D, Lopez L, Kosmatka M, DePinho R A, Cantley L C .2004. The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell, 6: 91~99
Shayesteh L, Lu Y, Kuo W L, Baldocchi R, Godfrey T, Collins C, Pinkel D, Powell B, Mills G B, Gray J W. 1999. PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet, 21: 99~102
Smith E J, Marie I, Prakash A, Garcia-Sastre A, Levy D E. 2001. IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein. J Biol Chem, 276(12): 8951~8957
Soulat D, Burckstummer T ,Westermayer S, Goncalves A, Bauch A, Stefanovic A, Hantschel O, Bennett K L, Decker T, Superti-furga G. 2008. The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response. EMBO J, 27(15): 2135~2146
Staal S P. 1987. Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci U S A, 84: 5034~5037
Steck P A, Pershouse M A, Jasser S A, Yung W K, Lin H, Ligon A H, Langford L A, Baumgard M L, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng D H, Tavtigian S V. 1997. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet, 15: 356~362
Steelman L S, Bertrand F E, McCubrey J A. 2004. The complexity of PTEN: mutation, marker and potential target for therapeutic intervention. Expert Opin Ther Targets, 8: 537~550
Stetson D B, Medzhitov R. 2006. Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. Immunity, 24: 93~103
Sujobert P, Bardet V, Cornillet-Lefebvre P, Hayflick J S, Prie N, Verdier F. 2005. Essential role for the p110δisoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia. Blood, 106: 1063~1066
Sun Q, Sun L, Liu H H, Chen X, Seth R B. 2006. The specific and essential role of MAVS in antiviral innate immune responses. Immunity, 24: 633~642
Suzuki A, de la Pompa J L, Stambolic V, Elia A J, Sasaki T, del B B, Ho A I, Wakeham A, Itie A, Khoo W, Fukumoto M, Mak T W. 1998. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol, 8: 1169~1178
Tait S W, Reid E B, Greaves D R, Wileman T E, Powell P P. 2000. Mechanism of inactivation of NF-kappa B by a viral homologue of I kappa b alpha. Signal-induced release of ikappa b alpha results in binding of the viral homologue to NF-kappa B. J Biol Chem, 275(44): 34656~34664
Takahashi K, Kawai T, Kumar H, Sato S, Yonehara S, Akira S. 2006. Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded RNA. J Immunol, 176: 4520~4524
Takahasi K, Yoneyama M, Nishihori T, Hirai R, Kumeta H, Narita R, Gale M Jr, Inagaki F, Fujita T. 2008. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. Mol Cell, 29: 428~40
Takaishi H, Konishi H, Matsuzaki H, Ono Y, Shirai Y, Saito N, Kitamura T, Ogawa W, Kasuga M, Kikkawa U, Nishizuka Y. 1999. Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B. Proc Natl Acad Sci USA, 96: 11836~11841
Takaoka A, Wang Z C, Choi M K, Yanai H, Negishi H, Ban T, Lu Y, Miyagishi M, Kodama T, Honda K, Ohba Y, Taniguchi T. 2007. DAI (DLM-1 ? ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature, 448: 501~505
Tang E D, Nunez G., Barr F G, Guan K L. 1999. Negative regulation of the forkhead transcription factor FKHR by Akt. J Biol Chem, 274: 16741~16746
Tattoli I, Carneiro L A, Jehanno M, Magalhaes J G, Shu Y, Philpott D J, Arnoult D, Girardin S E. 2008.
Tee A R, Blenis J. 2005. mTOR, translational control and human disease. Semin Cell Dev Biol, 16: 29~37 terminal differentiation in human melanoma cells. Gene, 236: 125~131
Thomas C C, Deak M, Alessi D R, van Aalten D M. 2002. High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate. Curr Biol, 12: 1256~1262
Thompson J E, Thompson C B. 2004. Putting the rap on Akt. J Clin Oncol, 22:4217~4226
Ting J P, Willingham S B, Bergstralh D T. 2008. NLRs at the intersection of cell death and immunity. Nat Rev Immunol, 8: 372~9
Tran H, Brunet A, Grenier J M, Datta S R, Fornace A J, DiStefano P S, Chiang L W, Greenberg M E. 2002. DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Science, 296: 530~534
Tran H, Brunet A, Griffith E C, Greenberg M E. 2003. The many forks in FOXO’s road. Sci STKE 172: Uematsu S, Akira S. 2007. Toll-like receptors and type I interferons. J Biol Chem, 282: 15319~23
Valchanova R S, Picard-Maureau M, Budt M, Brune W. 2006. Murine cytomegalovirus m142 and m143 are both required to block protein kinase R mediated shutdown of protein synthesis. J Virol, 80(20): 10181~10190
Venkataraman T, Valdes M, Elsby R, Kakuta S, Caceres G, Saijo S, Iwakura Y, Barber G N. 2007. Loss of DExD ? H box RNA helicase LGP2 manifests disparate antiviral responses. J Immunol, 178: 6444 ~ 6455
Vivanco I, Sawyers C L. 2002. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer, 2: 489~501
Vogt P K, Jiang H, Aoki M. 2005. Triple layer control: phosphorylation, acetylation and ubiquitination of FOXO proteins. Cell Cycle, 4: 908~913
vom Baur E, Zechel C, Heery D, Heine M J, Garnier J M, Vivat V, Le Douarin B, Gronemeyer H, Chambon P, Losson R. 1996. Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1. EMBO J, 15: 110~124
Wang X, Beugnet A, Murakami M, Yamanaka S, Proud C G. 2005. Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins. Mol Cell Biol, 25: 2558~2572
Wang Y Y, Li L, Han K J, Zhai Z, Shu H B. 2004. A20 is a potent inhibitor of TLR3- and Sendai virus -induced activation of NF-kappaB and ISRE and IFN-beta promoter. FEBS Lett, 576: 86~90
Wang Y, Helland A, Holm R, Kristensen G. B, Borresen-Dale A L. 2005. PIK3CA mutations in advanced ovarian carcinomas. Hum Mutat, 25: 322
Wang Y, Zhang H X, Sun Y P, Liu Z X, Liu X S, Wang L, Lu S Y, Kong H, Liu Q L, Li X H, Lu Z Y, Chen S J, Chen Z, Bao S S, Dai W, Wang Z G. 2007. Rig-I?/? mice develop colitis associated with downregulation of G alpha i2. Cell Res, 17: 858~68
Wang Z Y, Sun G L, Lu J X, Gu L J, Huang M E, Chen S R. 1990. Treatment of acute promyelocytic leukemia with all-trans retinoic acid in China. Nouv Rev Fr Hematol, 32: 34~36
Warrell R P, Frankel S R, Miller W H, Scheinberg D A, Itri L M, Hittelman W N, Vyas R, Andreeff M, Tafuri A, Jakubowski A. 1991. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). New Engl J Med, 324: 1385~1393
Wendel H G, De Stanchina E, Fridman J S, Malina A, Ray S, Kogan S, Cordon-Cardo C, Pelletier J, Lowe S W. 2004. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature, 428:332~7
Wertz I E, O’Rourke K M, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone D L, Ma A, Koonin E V, Dixit V M. 2004. Deubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature, 430: 694~9
Whiteman E L, Cho H, Birnbaum M J. 2002. Role of Akt/protein kinase B in metabolism. Trends Endocrinol Metab, 13: 444~451
Willment J A, Brown G D. 2008. C-type lectin receptors in antifungal immunity. Trends Microbiol, 16: 27~32
Wullschleger S, Loewith R, Hall M N. 2006. TOR signaling in growth and metabolism. Cell, 124: 471~484
Xia C, Meng Q, Cao Z, Shi X, Jiang B H. 2006. Regulation of angiogenesis and tumor growth by p110 alpha and AKT1 via VEGF expression. J Cell Physiol, 209: 56~66
Xiang Y, Condit R C, Vijaysri S, Jacobs B, Williams B R., Silverman R H. 2002. Blockade of interferon induction and action by the E3L double-stranded RNA binding proteins of vaccinia virus. J Virol, 76(10): 5251~5259
Xu L G, Wang Y Y, Han K J, Li L Y, Zhai Z, Shu H B. 2005. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell, 19: 727~40
Xu Q, Simpson S E, Scialla T J, Bagg A, Carroll M. 2003. Survival of acute myeloid leukemia cells requires PI3 kinase activation. Blood, 102: 972~980
Yamamoto S, Tomita Y, Hoshida Y, Morooka T, Nagano H, Dono K, Umeshita K, Sakon M, Ishikawa O, Ohigashi H, Nakamori S, Monden M, Aozasa K. 2004. Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma. Clin Cancer Res, 10: 2846~2850
Yang H, Zhao R, Yang H Y, Lee M H. 2005a. Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity. Oncogene, 24: 1924~1935
Yang Y, Liang Y, Qu L, Chen Z, Yi M, Li K, Lemon S M. 2007. Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor. Proc Natl Acad Sci U S A, 104(17): 7253~7258
Yoneyama M, Fujita T. 2008. Structural mechanism of RNA recognition by the RIGI-like receptors. Immunity, 29(2): 178~181
Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M Jr, Akira S, Yonehara S, Kato A, Fujita T. 2005. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA-5, and LGP2 in antiviral innate immunity. Immunol, 175(5): 2851~2858
Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T. 2004. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol, 5(7): 730~737
Zacchi P, Gostissa M, Uchida T, Salvagno C, Avolio F, Volinia S, Ronai Z, Blandino G, Schneider C, Del Sal G. 2002. The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults. Nature, 419: 853~7
Zeng Y W, agner E J, Cullen B R. 2002. Both natural and designed microRNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell, 9:1327
Zhang M, Wu X, Lee A J, Jin W, Chang M, Wright A, Imaizumi T, Sun S C. 2008. Regulation of IKK related kinases and antiviral responses by tumor suppressor CYLD. J Biol Chem, 283(27): 18621~6
Zhang N N, Shen S H, Jiang L J, Zhang W, Zhang H X, Sun Y P, Li X Y, Huang Q H, Ge B X, Chen S J, Wang Z G, Chen Z, Zhu J. 2008. RIG-I plays a critical role in negatively regulating granulocytic proliferation. Proc Natl Acad Sci USA, 105(30): 10553~10558
Zhao X, Gan L, Pan H, Kan D, Majeski M, Adam S A, Unterman T G. 2004. Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14-3-3-dependent and -independent mechanisms. Biochem J, 378, 839~849
Zheng H, You H, Zhou X Z, Murray S A, Uchida T, Wulf G, Gu L, Tang X, Lu K P, Xiao Z X. 2002. The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature, 419: 849~53
Zheng P Z, Wang K K, Zhang Q Y, Huang Q H, Du Y Z, Zhang Q H, Xiao D K, Shen S H, Imbeaud S, Eveno E, Zhao C J, Chen Y L, Fan H Y, Waxman S, Auffray C, Jin G, Chen S J. 2005. Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A, 102: 7653~7658
Zhou G, Zhang J, Wang Z, Chen S, Chen Z. 2007. Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy. Phil Trans R Soc B, 362: 959~971
Zubilewicz A, Hecquet C, Jeanny J C, Soubrane G, Courtois Y, Mascarelli F. 2001. Two distinct signalling pathways are involved in FGF2-stimulated proliferation of choriocapillary endothelial cells: a comparative study with VEGF. Oncogene, 20: 1403~1413
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