USP22通过SIRT1-STAT3/MMP9通路抑制结肠癌细胞的侵袭能力
摘要
泛素特异肽酶22(ubiquitin-specific processing peptidase22, USP22)为hSAGA (human Spt-Ada-Gcn5-acetyltransferase)转录辅助因子复合物的亚基,通过对组蛋白尾部的特定氨基酸去泛素化修饰使转录复合物进入到目标基因启动子上,激活基因转录。USP22作用广泛,主要包括三大类功能：一,USP22去泛素化相关蛋白,包括SIRT1、 FUBP1、 IRF1、 TRF1等。USP22通过与这些蛋白作用进一步调控其下游靶基因/蛋白。二,USP22直接激活一些基因的转录。ChIP证明USP22与Myc靶基因CDCA7、 CyclinD2、 ODC、CAD、 MTA1的启动子区结合并激活这些基因转录。三,USP22直接或间接与一些基因的表达相关,包括BMI-1、 c-Myc、 pAkt、 p16INK4a、 p14ARF、 CyclinD2、 p53、 p21等。一组包含11个基因的癌死亡标签(death-from-cancer signature)的高度表达能够鉴别出有治疗耐药、复发和远处转移等特性的恶性肿瘤细胞,USP22为其中之一。USP22促进多种肿瘤细胞系增殖、抑制细胞凋亡,并且通过去泛素化SIRTl抑制结肠癌细胞凋亡。本研究探讨USP22对STAT3的影响及其对结肠癌细胞侵袭能力的作用。
首先,本研究在模式工具细胞293T中转染四种表达质粒的不同组合,在强化表达体系(不同蛋白有足够多的量来研究蛋白间相互作用)中通过免疫共沉淀、Western Blotting验证了USP22去泛素化SIRT1、SIRT1去乙酰化STAT3; Western Blotting证实USP22可借助SIRT1降低STAT3乙酰化水平。接下来,本研究检测了6株结肠癌细胞系中USP22的表达,选用高表达USP22的结肠癌细胞HCT116、 HT29、SW480,其中结肠癌细胞系HT29、 SW480中通过免疫共沉淀、Western blotting等方法研究USP22和SIRT1、STAT3之间的关系,发现抗USP22抗体免疫沉淀的蛋白中可检测到STAT3,表明USP22与STAT3存在内源性相互作用。同时,HT29、 SW480细胞中用强化表达体系发现过表达SIRT1时,USP22与STAT3之间的作用增强,说明USP22、 SIRT1、 STAT3三种蛋白以复合体形式存在。HT29、 SW480细胞中USP22同样通过SIRT1降低STAT3乙酰化水平,这阐明了USP22/SIRT1/STAT3之间存在的表观遗传调控方式。
其次,本研究用siRNA干扰技术在体外有效敲低USP22在结肠癌细胞HT29、SW480中的表达,发现SIRT1表达下调、STAT3的乙酰化水平升高、STAT3促进肿瘤侵袭方面的靶基因TWIST、MMP9表达升高,而STAT3mRNA和蛋白水平并没有改变,说明USP22通过去泛素化SIRT1这种表观遗传机制下调STAT3乙酰化水平、影响STAT3的转录活性。同时,Real Time PCR、Transwell细胞侵袭实验等证实HT29、 SW480细胞中联合敲低USP22/STAT3之后TWIST/MMP9mRNA水平、细胞体外侵袭能力较单独敲低STAT3明显升高。因此,本研究首次证明了USP22可通过SIRT1/STAT3/MMP9通路影响结肠癌细胞的侵袭能力。此外,39例结肠癌组织芯片中检测USP22的表达与STAT3表达(总蛋白)成中度正相关(r=0.457P<0.01),与MMP9表达成低度正相关(r=0.385P<0.05)而STAT3表达与MMP9表达高度相关(r=0.785,P<0.01)。同时我们在结肠癌侵袭前沿观察到USP22低表达、MMP9滴状高表达,说明USP22表达下降可负向调控MMP9表达以及结肠癌的侵袭,这与我们体外研究的结果一致。
总之,我们的研究首次揭示了USP22与SIRT1、 STAT3形成蛋白复合体,并且USP22通过SIRT1/STAT3/MMP9途径抑制结肠癌细胞的侵袭,本研究加深了USP22生物学功能的理解以及USP22在结肠癌细胞侵袭中作用的认识。
USP22(ubiquitin-specific processing peptidase22) is a subunit of hSAGA (human Spt-Ada-Gcn5-acetyltransferase) co-activator complex. Within hSAGA, USP22deubiquitylates histone H2A and H2B to regulate the transcription and expression of the related genes. USP22is involved in three categories of cellular functions. First, deubiquitination of related proteins, such as SIRT1, FUBP1, IRF1, TRF1. Second, transcriptional regulation of specific genes. USP22is recruited to Myc target genes CDCA7, CyclinD2, ODC, CAD, MTA1by Myc oncoprotein. Third, USP22is related with expression of some genes directly or indirectly, such as BMI-1, c-Myc, pAkt, p16INK4a, p14ARF, CyclinD2, p53, p21. Now that it is believed that USP22is one of the death-from-cancer signature and associated with proliferation, distant metastasis and poor prognosis. USP22could promote tumor proliferation and suppress tumor cell apoptosis. USP22de-ubiquitinates SIRT1to suppress colon cancer cell apoptosis. In this research, we report a new mechanism by which USP22affects SIRT1-STAT3pathway and colon cancer invasion.
First, to explore protein-protein interaction,293T cells were employed as cellular model with force-rexpressed system (assuring there is enough amount of proteins) to observe protein-protein interaction. As was proved, USP22could deubiquitinate SIRT1and SIRT1down regulates STAT3acetylation, four plasmids in different combination were transfected in293T cells to certify the USP22-SIRT1-STAT3interaction. We found USP22could down regulate STAT3acetylation through SIRT1. Then we screened USP22expression in6colon cancer cells and HT29, SW480cells with high-expression of USP22were picked up for the following research. To demonstrate USP22-SIRT1-STAT3interaction, co-immuno-precipitation and western blotting were used again. STAT3interaction with USP22was shown by anti-USP22antibody pull down and the detection of STAT3using an anti-STAT3antibody in HT29, SW480cells, suggesting that endogenous USP22 interacts with endogenous STAT3. The interaction of USP22and STAT3was strengthened in SIRT1-overexpressed cells, suggesting USP22interacts with STAT3mediated by SIRT1and USP22, STAT3, SIRT1are also present in a single protein complex. Then we found USP22could down regulate STAT3acetylation through SIRT1in HT29, SW480cells. Therefore our research demostrated the presence of USP22/SIRT1/STAT3pahtway and clarified the epigenetic mechanism of their interaction
Second, depletion of endogenous USP22by RNA interference in HT29, SW480cells destabilized SIRT1and elevated STAT3acetylation. USP22knockdown also promoted expression of STAT3target genes MMP9and TWIST, which are involved in tumor invasion, but STAT3expression was not affected, confirming USP22antagonizes the STAT3transcription activation by deacetylation of STAT3at posttranscriptional level. USP22/STAT3co-depletion partly rescued reduced MMP9and TWIST mRNA levels as well as cell invasion, induced by STAT3depletion alone, which were tested by Real Time PCR and Transwell assay. Therefore, for the first time, we identified USP22affects colon cancer cell invasion by SIRT1/STAT3/MMP9pathway. USP22expression positively correlated with STAT3expression (r=0.457, P<0.01) and MMP9expression (r=0.385, P＜0.05); STAT3expression positively correlated with MMP9expression (r=0.785, P＜0.01) in colon cancer TMA including39patients. In the mean time, we observed that USP22expression was lower in the leading area of colon caner invasion compared to colon cancer, but MMP9expression was higher, suggesting USP22may downregulate MMP9expression and colon cancer invasion.
In conclusion, our study reveals USP22, SIRT1, STAT3are present in a single protein complex,and elucidates that USP22could suppress colon cancer cell invasion by SIRT1/STAT3/MMP9pathway. The research broaden our knowledge about the biological function of USP22and its role in colon cancer invasion.
首先,本研究在模式工具细胞293T中转染四种表达质粒的不同组合,在强化表达体系(不同蛋白有足够多的量来研究蛋白间相互作用)中通过免疫共沉淀、Western Blotting验证了USP22去泛素化SIRT1、SIRT1去乙酰化STAT3; Western Blotting证实USP22可借助SIRT1降低STAT3乙酰化水平。接下来,本研究检测了6株结肠癌细胞系中USP22的表达,选用高表达USP22的结肠癌细胞HCT116、 HT29、SW480,其中结肠癌细胞系HT29、 SW480中通过免疫共沉淀、Western blotting等方法研究USP22和SIRT1、STAT3之间的关系,发现抗USP22抗体免疫沉淀的蛋白中可检测到STAT3,表明USP22与STAT3存在内源性相互作用。同时,HT29、 SW480细胞中用强化表达体系发现过表达SIRT1时,USP22与STAT3之间的作用增强,说明USP22、 SIRT1、 STAT3三种蛋白以复合体形式存在。HT29、 SW480细胞中USP22同样通过SIRT1降低STAT3乙酰化水平,这阐明了USP22/SIRT1/STAT3之间存在的表观遗传调控方式。
其次,本研究用siRNA干扰技术在体外有效敲低USP22在结肠癌细胞HT29、SW480中的表达,发现SIRT1表达下调、STAT3的乙酰化水平升高、STAT3促进肿瘤侵袭方面的靶基因TWIST、MMP9表达升高,而STAT3mRNA和蛋白水平并没有改变,说明USP22通过去泛素化SIRT1这种表观遗传机制下调STAT3乙酰化水平、影响STAT3的转录活性。同时,Real Time PCR、Transwell细胞侵袭实验等证实HT29、 SW480细胞中联合敲低USP22/STAT3之后TWIST/MMP9mRNA水平、细胞体外侵袭能力较单独敲低STAT3明显升高。因此,本研究首次证明了USP22可通过SIRT1/STAT3/MMP9通路影响结肠癌细胞的侵袭能力。此外,39例结肠癌组织芯片中检测USP22的表达与STAT3表达(总蛋白)成中度正相关(r=0.457P<0.01),与MMP9表达成低度正相关(r=0.385P<0.05)而STAT3表达与MMP9表达高度相关(r=0.785,P<0.01)。同时我们在结肠癌侵袭前沿观察到USP22低表达、MMP9滴状高表达,说明USP22表达下降可负向调控MMP9表达以及结肠癌的侵袭,这与我们体外研究的结果一致。
总之,我们的研究首次揭示了USP22与SIRT1、 STAT3形成蛋白复合体,并且USP22通过SIRT1/STAT3/MMP9途径抑制结肠癌细胞的侵袭,本研究加深了USP22生物学功能的理解以及USP22在结肠癌细胞侵袭中作用的认识。
USP22(ubiquitin-specific processing peptidase22) is a subunit of hSAGA (human Spt-Ada-Gcn5-acetyltransferase) co-activator complex. Within hSAGA, USP22deubiquitylates histone H2A and H2B to regulate the transcription and expression of the related genes. USP22is involved in three categories of cellular functions. First, deubiquitination of related proteins, such as SIRT1, FUBP1, IRF1, TRF1. Second, transcriptional regulation of specific genes. USP22is recruited to Myc target genes CDCA7, CyclinD2, ODC, CAD, MTA1by Myc oncoprotein. Third, USP22is related with expression of some genes directly or indirectly, such as BMI-1, c-Myc, pAkt, p16INK4a, p14ARF, CyclinD2, p53, p21. Now that it is believed that USP22is one of the death-from-cancer signature and associated with proliferation, distant metastasis and poor prognosis. USP22could promote tumor proliferation and suppress tumor cell apoptosis. USP22de-ubiquitinates SIRT1to suppress colon cancer cell apoptosis. In this research, we report a new mechanism by which USP22affects SIRT1-STAT3pathway and colon cancer invasion.
First, to explore protein-protein interaction,293T cells were employed as cellular model with force-rexpressed system (assuring there is enough amount of proteins) to observe protein-protein interaction. As was proved, USP22could deubiquitinate SIRT1and SIRT1down regulates STAT3acetylation, four plasmids in different combination were transfected in293T cells to certify the USP22-SIRT1-STAT3interaction. We found USP22could down regulate STAT3acetylation through SIRT1. Then we screened USP22expression in6colon cancer cells and HT29, SW480cells with high-expression of USP22were picked up for the following research. To demonstrate USP22-SIRT1-STAT3interaction, co-immuno-precipitation and western blotting were used again. STAT3interaction with USP22was shown by anti-USP22antibody pull down and the detection of STAT3using an anti-STAT3antibody in HT29, SW480cells, suggesting that endogenous USP22 interacts with endogenous STAT3. The interaction of USP22and STAT3was strengthened in SIRT1-overexpressed cells, suggesting USP22interacts with STAT3mediated by SIRT1and USP22, STAT3, SIRT1are also present in a single protein complex. Then we found USP22could down regulate STAT3acetylation through SIRT1in HT29, SW480cells. Therefore our research demostrated the presence of USP22/SIRT1/STAT3pahtway and clarified the epigenetic mechanism of their interaction
Second, depletion of endogenous USP22by RNA interference in HT29, SW480cells destabilized SIRT1and elevated STAT3acetylation. USP22knockdown also promoted expression of STAT3target genes MMP9and TWIST, which are involved in tumor invasion, but STAT3expression was not affected, confirming USP22antagonizes the STAT3transcription activation by deacetylation of STAT3at posttranscriptional level. USP22/STAT3co-depletion partly rescued reduced MMP9and TWIST mRNA levels as well as cell invasion, induced by STAT3depletion alone, which were tested by Real Time PCR and Transwell assay. Therefore, for the first time, we identified USP22affects colon cancer cell invasion by SIRT1/STAT3/MMP9pathway. USP22expression positively correlated with STAT3expression (r=0.457, P<0.01) and MMP9expression (r=0.385, P＜0.05); STAT3expression positively correlated with MMP9expression (r=0.785, P＜0.01) in colon cancer TMA including39patients. In the mean time, we observed that USP22expression was lower in the leading area of colon caner invasion compared to colon cancer, but MMP9expression was higher, suggesting USP22may downregulate MMP9expression and colon cancer invasion.
In conclusion, our study reveals USP22, SIRT1, STAT3are present in a single protein complex,and elucidates that USP22could suppress colon cancer cell invasion by SIRT1/STAT3/MMP9pathway. The research broaden our knowledge about the biological function of USP22and its role in colon cancer invasion.
引文
[1].Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet.2013,6736(13):61649-9
[2].Gralnek IM, Siersema PD, Halpern Z, et al. Standard forward-viewing colonoscopy versus full-spectrum endoscopy:an international, multicentre, randomised, tandem colonoscopy trial[J]. Lancet Oncol,2014,15(3):353-60.
[3].Glinsky GV, Berezovska O, Glinskii AB, et al. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer[J]. J Clin Invest,2005,115(6):1503-1521.
[4].Glinsky GV. Genomic models of metastatic cancer:funtional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated Polycomb Group (PcG)protein chromatin silencing pathway[J]. Cell Cycle,2006,5(11): 1208-1216.
[5].Lee HJ,Kim MS, Shin JM, et al. The expression patterns of deubiquitinating enzymes,USP22and Usp22[J]. Gene ExpressionPatterns 6,2006,6(3):277-284.
[6].Xiao YZ, Harla KP, Alan WT, et al. USP22, An hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquity lation of histone H2A[J]. Cell Cycle,2008,7(11):1522-1524.
[7].Zhang X-Y, Varthi M, Sykes SM, et al. The Putative Cancer Stem Cell Marker USP22 Is a Subunit of the Human SAGA Complex Required for Activated Transcription and Cell-Cycle Progression[J]. Mol Cell,2008,29(1):102-111.
[8].Liu YL, Jiang SX, Yang YM, et al.USP22 Acts as an Oncogene by the Activation of BMI-1-Mediated INK4a/ARF Pathway and Akt Pathway[J]. Cell Biochem Bio-phys,2012,62(1):229-35.
[9].Xu H, Liu YL, Yang Ym, et al. Knock-down of ubiquitin-specific protease 22 by micro-RNA interference inhibits colorectal cancer growth[J]. International Journal of Colorectal Disease,2012,27(1):21-30.
[10].Guney, I., Wu, S., and Sedivy, J.M. Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and pl6(INK4a)[J]. Proc Natl Acad Sci USA,2006,103(10):3645-3650.
[11].Kim JH, Yoon SY, Kim CN, et al. The Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlateswith the reduced p16 INK4a/p14ARF protein[J]. Cancer Lett,2004,203 (2):217-224.
[12].Sridharan R, Tchieu J, Mason MJ, et al. Role of the murine reprogramming factors in the induction of pluripotency[J]. Cell,2009,136(2):364-77.
[13].Sussman RT, Stanek TJ, Esteso P, et al. The epigenetic modifier ubiquitin-specific protease 22 (USP22) regulates embryonic stem cell differentiation via transcriptional repression of sex-determining region Y-box 2 (SOX2)[J]. J Biol Chem,2013,288(33):24234-46.
[14].Lin Z, Yang H, Kong Q, et al.USP22 antagonizes p53 transcriptional activation by deubiquitinating Sirtl to suppress cell apoptosis and isrequired for mouse embryonic development[J], Mol Cell.2012,46(4):484-94.
[15].Rahman S, Islam R. Mammalian Sirtl:insights on its biological functions[J]. Cell Communication and Signaling,2011,9:11.
[16].Hajji N, Wallenborg K, Vlachos P, et al. Opposing effects of hMOF and SIRT1 on H4K16 acetylation and the sensitivity to the topoisomerase II inhibitor etoposide[J]. Oncogene,2010,29(15):2192-204.
[17].Jung-Hynes B, Ahmad N. Role of p53 in the anti-proliferative effects of Sirtl inhibition in prostate cancer cells[J]. Cell Cycle,2009,8(10):1478-1483.
[18]Dai JM, Wang ZY, Sun DC, et al. SIRT1 interacts with p73 and suppresses 73-dependent transcriptional activit[J]. J Cell Physiol,2007,210(1):161-166.
[19].Sedding DG. FoxO transcription factors in oxidative stress response and ageing-a new fork on the way to longevity? [J]. Biol Chem,2008, 389(3):279-283.
[20].Fu M, Liu M, S auve AA, et al. Hormonal control of androgen recept or function through SIRT1[J]. Mol Cell Biol,2006,26(21):8122-8135.
[21].Wang C, Chen L, Hou X, et al. Interactions between E2F 1 and SirTl regulate apoptotic response to DNA damage[J]. Nat Cell Biol,2006,8(9):1025-1031.
[22].Ghosh HS, McBurney M, Robbins PD. SIRT1 negatively regulates the mammalian target of rapamycin[J]. PLoS One,2010,5(2):e9199.
[23].Yuan J, Minter-Dykhouse K, Lou Z. A c-Myc-SIRT1 feedback loop regulates cell growth and transformation[J]. J Cell Biol.2009 Apr 20;185(2):203-11.
[24].Firestein R, Blander G, Michan S,et al. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth[J]. PLoS One.2008,3(4):e2020.
[25].Lim JH, Lee YM, Chun YS, et al. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor lalpha[J]. Mol Cell.2010, 38(6):864-78.
[26].Blander G, Guarente L. The Sir2 family of protein deacetylases[J]. Annu Rev Biochem,2004,73(2):417-435.
[27].Tao Liu, Pei Y. Liu, Glenn M. Marshall. The Critical Role of the Class III Histone Deacetylase SIRT1[J]..Cancer Res,2009,69 (5):1702-1705.
[28].Bradbury CA, Khanim FL, Hayden R, et al. Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors[J]. Leukemia,2005,19(10):1751-1759.
[29].Liu G, Yuan X, Zeng Z, et al. Analysis of gene expression and chemoresistance of CD133+cancer stem cells in glioblastoma[J]. Mol Cancer,2006,5:67.
[30].Huffman DM, Grizzle WE, Bamman MM, et al. SIRT1 is significantly elevated in mouse and human prostate cancer[J].Cancer Res,2007,67(14):6612-6618.
[31].Stunkel W, Peh BK, Tan YC,et al. Function of the SIRT1 protein deacetylase in cancer[J]. Biotechnol J,2007,2(11):1360-1368.
[32].Deng CX. SIRT1, Is It a Tumor Promoter or Tumor Suppressor?[J]. Int J Biol Sci,2009,5(2):147-152.
[33].Wang RH, Sengupta K, Li C, et al. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice[J]. Cancer Cell,2008, 14(4):312-323.
[34].Armour SM, Bennett EJ, Braun CR, et al. A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex[J]. Mol Cell Biol,2013,33(8):1487-502.
[35].Zhang J, Lee SM, Shannon S, et al. The type III histone deacetylase SIRT1 is essential for maintenance of T cell tolerance in mice[J]. J Clin Invest,2009, 119:3048-3058.
[36].Sestito R, Madonna S, Scarponi C, et al. STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a directinhibition of STAT3 acetylation[J]. FASEB J 2011,25(3):916-27.
[37].Ailfrey VG, Faulkner K, Mirsky AE. Acetrlation and Methylation of Histones and Their Possible Role in the Regulation of Rna Synthesis[J]. Proc Natl Acad Sci, 1964,51:786-794.
[38].Vidali G, Boffa LC, Bradbury EM, et al. Butyrate suppression of histone deacetyrlation leads to accumulation of multiacetylated forms of histones H3 and H4 and increased DNase I sensitivity of the associated DNA sequences [J]. Proe Natl Aead Sci,1978,75:2239-2243.
[39].Hebbes TR, Thorne AW, Crane-Robinson C. A direct link between core histone acetyrlation and transcriptionally active chromatin[J]. EMBO J,1988,7:1395-1402.
[40].Lee DY, Hayes JJ, Pruss D, et al. A positive role for histone acetylation in transcription factor access to nucleosomal DNA [J]. Cell,1993,72:73-84.
[41].Vettese-Dadey M, Grant PA, Hebbes TR, et al. Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro[J]. EMBO J,1996,15:2508-2518.
[42].Yuan ZL, Guan YJ, Chatterjee D, et al. Stat3 dimerization regulated by reversible acetylation of a single lysine residue [J]. Science,2005,307:269-273
[43].O'Shea JJ, Kanno Y, Chen X, et al. Cell signaling. Stat acetylation-a key facet of cytokine signaling?[J]. Science,2005,307:217-218.
[44].Varinou L, Ramsauer K, Karaghiosoff M, et al. Phosphorylation of the Statl transactivation domain is required for full-fledged IFN-gamma-dependent innate immunity[J]. Immunity,2003,19:793-802.
[45].Levy DE, Darnell JE, Jr. Stats:transcriptional control and biological impact[J]. Nat Rev Mol Cell Biol,2002,3:651-662. [46].Shuai K. Serine phosphorylation:arming Stati against infection[J]. Immunity, 2003,19:771-772
[47].Alvarez JV, Frank DA. Genome-wide analysis of STAT3 target genes: elucidating the mechanism of STAT-mediated oncogenesis[J]. Cancer Biol Ther 2004, 3(11):1045-50.
[48].Bugno M, Graeve L, Gatsios P, et al. Identification of the interleukin-6/oncostatin M response element in the rat tissue inhibitor of metalloproteinases-1 (TIMP-1) promoter[J]. Nuc Acids Res,1995,23:5041-5047.
[49].Cheng GZ, Zhang WZ, Sun M, Wang Q, Coppola D, et al. Twist is transcriptionally induced by activation of STAT3 and mediates STAT3 oncogenic function[J]. J Biol Chem 2008,283:14665-14673.
[50].Niu G, Briggs J, Deng J, et al. Signal transducer and activator of transcription 3 is required for hypoxia-inducible factor-1 alpha RNA expression in both tumor cells and tumor-associated myeloid cells[J]. Mol Cancer Res,2008,6:1099-105.
[51].Niu G, Wright KL, Huang M, et al. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis[J]. Oncogene,2002,21:2000-8.
[52].Zhang M, Liu Y, Feng H, et al. CD133 affects the invasive ability of HCT116 cells by regulating TIMP-2[J]. Am J Pathol,2013,182(2):565-76.
[53].Kajita M, Itoh Y, Chiba T, et al. Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration[J]. J Cell Biol,2001,153(5):893-904.
[54].Spessotto P, Rossi FM, Degan M.et al. Hyaluronan-CD44 interaction hampers migration of osteoclast-like cells by down-regulating MMP-9[J]. J CellBiol,2002, Biol.158(6):1133-44.
[55].Huth JR, Yu LP, Collins I, et al. NMR-Driven Discovery of Benzoylanthranilic Acid Inhibitors of Far Upstream Element Binding Protein Binding to the Human Oncogene c-myc Promoter[J]. J Med Chem,2004,47(20):4851-7.
[56].Atanassov BS, Dent SY. USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1[J]. Embo Reports,2011,12:924-930.
[57].Pankratz SL, Tan EY, Fine Y,et al. Insulin receptor substrate-2 regulates aerobic glycolysis in mouse mammary tumor cells via glucose transporter 1[J], J Biol Chem, 2009,284(4):2031-7.
[58].Liu P, Wilson MJ. miR-520c and miR-373 upregulate MMP9 expression by targeting mTOR and SIRT1, and activate theRas/Raf/MEK/Erk signaling pathway and NF-kB factor in human fibrosarcoma cells[J]. J Cell Physiol,2012,227(2):867-76.
[59].Liu Y, Yang Y, Xu H,et al. Implication of USP22 in the regulation of BMI-1, c-Myc, p16INK4a, p14ARF, and cyclin D2 expression in primary colorectal carcinomas[J]. Diagn Mol Patho,2010,19(4):194-200.
[60].Liu YL, Yang YM, Xu H, et al.Increased expression of ubiquitin-specific protease 22 can promote cancer progression and predict therapy failure in human colorectal cancer[J]. J Gastroenterol Hepatol.2010,25(11):1800-5.
[61].Liu YL, Yang YM, Xu H, et al. Aberrant expression of USP22 is associated with liver metastasis and poor prognosis of colorectal cancer [J]. J Sur Oncol,2011, 103(3):283-289.
[62].Li ZW, Liu YQ:Progress of targeted therapy related to K-ras mutation. Zhong Hua Bing Li Xue Za Zhi 2012; 41(1):59-61.
[63].Ohbayashi N, Ikeda O, Taira N, et al. LIF-and IL-6-induced acetylation of STAT3 at Lys-685 through PI3K/Akt activation[J]. Biol Pharm Bull,2007, 30(10):1860-4.
[64].Folkman J, Shing Y.Angiogenesis[J]. J Biol Chem,1992,267(16):10931-4.
[65].Takahashi Y, Kitadai Y, Bucana CD, et al. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer[J]. Cancer Res,1995,55(18):3964-8.
[66].Ma XT, Wang S, Ye YJ, et al. Constitutive activation of Stat3 signaling pathway in human colorectal carcinoma[J].World J Gastroenterol,2004,10(11):1569-73.
[67].Wei X, Wang G, Li W, et al. Activation of the JAK-STAT3 pathway is associated with the growth of colorectal carcinoma cells[J]. Oncol Rep,2014,31(1):335-41.
[68].Siveen KS1, Sikka S2, Surana R, et al. Targeting the STAT3 signaling pathway in cancer:Role of synthetic and natural inhibitors [J]. Biochim Biophys Acta,2014, 1845(2):136-154.
[69].Pratt SL, Ogle CK, Mao JX, et al.Interleukin-6 signal transduction in human intestinal epithelial cells [J].Shock,2000,13(6):435-40.
[70].Karpf AR, Peterson PW, Rawlins JT, et al.Inhibition of DNA methyltransferase stimulates the expression of signal transducer and activator oftranscription 1,2, and 3 genes in colon tumor cells[J]. Proc Natl Acad Sci USA,1999,96(24):14007-12.
[72].Orlovsky K, Theodor L, Malovani H, et al/Gamma interferon down-regulates Fer and induces its association with inactive Stat3 in coloncarcinoma cells [J]. Oncogene. 2002,21(32):4997-5001.
[73].Ma X, Wang S, Du R, et al.Stat3 signal transduction pathway orchestrates G1 to S cell cycle transition in colon cancer cells[J].Beijing Da Xue Xue Bao,2003, 35(l):50-3.
[74].Ma XT, Wang S, Ye YJ,et al.Relationship of Stat3 and its target gene products with malignancy in human colorectal carcinoma[J]. Ai Zheng,2003,22(11):1135-9.
[75].Herbeuval JP, Lelievre E, Lambert C, et al.Recruitment of STAT3 for production of IL-10 by colon carcinoma cells induced by macrophage-derived IL-6[J]. J Immunol, 2004,172(7):4630-6.
[76].Corvinus FM, Orth C, Moriggl R, et al.Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth[J]. Neoplasia. 2005,7(6):545-55.
[77].Atreya R, Neurath MF. Involvement of IL-6 in the pathogenesis of inflammatory bowel disease and colon cancer[J]. Clin Rev Allergy Immunol,2005,28(3):187-96.
[78].Lin Q, Lai R, Chirieac LR, Li C, et al. Constitutive activation of JAK3/STAT3 in colon carcinoma tumors and cell lines:inhibition of JAK3/STAT3 signaling induces apoptosis and cell cycle arrest of colon carcinoma cells[J]. Am J Pathol.2005 167(4):969-80.
[79].Becker C, Fantini MC, Schramm C, et al.TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling[J]. Immunity,2004, 21(4):491-501.
[80].Tomida M, Ohtake H, Yokota T, et al.Stat3 up-regulates expression of nicotinami-de N-methyltransferase in human cancer cells[J]. J Cancer Res Clin Oncol. 2008,134(5):551-9.
[81].Tsareva SA, Moriggl R, Corvinus FM, et al.Signal transducer and activator of transcription 3 activation promotes invasive growth of coloncarcinomas through matrix metalloproteinase induction[J]. Neoplasia.2007,9(4):279-91.
[82].Valdes-Mora F, Gomez del Pulgar T, Bandres E, et al. TWIST1 overexpression is associated with nodal invasion and male sex in primary colorectalcancer[J]. Ann Surg Oncol,2009,16(1):78-87
[83].Gavert N, Vivanti A, Hazin J, et al. L1-mediated colon cancer cell metastasis does not require changes in EMT and cancer stem cell markers[J]. Mol Cancer Res, 2011,9(1):14-24.
[84].Qi L, Sun B, Liu Z, et al. Dickkopf-1 inhibits epithelial-mesenchymal transition of colon cancer cells and contributes to colon cancer suppression[J]. Cancer Sci,2012, 103(4):828-35
[85].Lv Q, Wang W, Xue J, et al. DEDD interacts with PI3KC3 to activate autophagy and attenuate epithelial-mesenchymal transition in human breast cancer[J]. Cancer Res,2012,72(13):3238-50
[86].Pawelek JM, Chakraborty AK. The cancer cell--leukocyte fusion theory of metastasis[J]. Adv Cancer Res,2008,101:397-444.
[87].Celesti G, Di Caro G, Bianchi P, et al. Presence of Twistl-positive neoplastic cells in the stroma of chromosome-unstable colorectal tumors [J]. Gastroenterology, 2013,145(3):647-57
[88].Singh N, Liu G, Chakrabarty S. Isolation and characterization of calcium sensing receptor null cells:a highly malignant and drug resistant phenotype of colon cancer[J].Int J Cancer,2013,132(9):1996-2005
[89].Pelaez-Garcia A, Barderas R, Torres S, et al. PFGFR4 role in epithelial-mesenchymal transition and its therapeutic value in colorectal cancer [J]. PLoS One.2013,8(5):e63695.
[90].Meng XN, Jin Y, Yu Y, et al.Characterisation of fibronectin-mediated FAK signalling pathways in lung cancer cell migration andinvasion[J]. Br J Cancer.2009, 101(2):327-34.
[91].Loesch M, Zhi HY, Hou SW, et al.p38gamma MAPK cooperates with c-Jun in trans-activating matrix metalloproteinase 9[J]. J Biol Chem.2010,285(20):15149-58.
[92].Park KS, Kim SJ, Kim KH, et al.Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer[J].J Gastroenterol Hepatol,2011, 26(2):391-7
[93].Li D, Sun X, Yan D, Piwi12 modulates the proliferation and metastasis of colon cancer via regulation of matrix metallopeptidase 9 transcriptional activity [J].Exp Biol Med (Maywood),2012,237(10):1231-40.
[94].Park KS, Kim SJ, Kim KH, et al.Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer[J]. J Gastroenterol Hepatol,2011, 26(2):391-7.
[1].Sun, ZW, Allis CD. The language of covalent histone modications[J]. Nature,2002, 403(6765):41-45.
[2].Goldknopf I, Taylor CW, Baum RM et al. Isolation and characterization of proteinA 24, a "histone-like"non-histonechromosomal protein[J]. J Biol Chem,1975, 250(18):7182-7187
[3].Robzyk K, Recht J, Osley MA. Rad6-dependentubiquitination of histone H2B in yeast[J]. Science,2000,287(5452):501-504.
[4].Matsui SI, Seon BK, Sandberg AA et al. Disappearanceof a structural chromatin proteinA 24 in mitosis implications for molecular basis of chromatincondensatio[J]. Proc Natl Acad Sci,1979,76(12):6386-6390.
[5].Wang H.,Wang L, Erdjument-Bromage H, et al. Role of histone H2A ubiquitination in Polycomb silencing[J]. Nature,2004,431(7010):873-878.
[6].Cao R.,Tsukada Y, Zhang Y, et al. Role of Bmi-1 and RinglA in H2A ubiquitylation and Hoxgene silencing[J]. Mol Cell,2005,20(6):845-854.
[7].Buchwald G, van de rStoop P, Weichenrieder O,et al. Structure and E3-ligase activity of the ring-ring complex of polycomb proteins Bmil and Ringlb[J]. EMBO J, 2006,25(11):2465-2474.
[8].Chen A, Kleiman FE, Manley JL, et al. Autoubiquitination of the BRCA1* BARD1 RING ubiquitin ligase[J]. J Biol Chem,2002,277(24):22085-22092.
[9].de Napoles M, Mermoud JE, Wakao R, et al. Polycombgroup proteins Ring1 A/Blink ubiquitylation of histone H2A to heritable gene silencing and X inactivatio[J]. Dev Cell,2004,17(5):663-676.
[10].Stock JK, Giadrossi S, Casanova M et al.Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase Ⅱ at bivalent genes in mouse ES cells [J]. Nat Cell Biol,2007,9(12):1428-35.
[11].Robzyk K, RechtJ, Osley MA. Rad6-dependentubiquitination of histone H2B in yeast[J].Science,2000,287(5452):501-504.
[12].Hwang WW, Venkatasubrahmanyam S, Ianculescu AG, et al. A conserved RING finger protein required for histone H2B monoubiquitination and cell size contro[J]. Mol Cell,2003,11(1):261-6.
[13].Wood A, Krogan NJ, Dover J,et al. Brel, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter[J]. Mol Cell,2003, 11(1):267-74.
[14].Kao CF, Hillyer C, Tsukuda T, et al. Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B[J]. Genes Dev,2004,18(2):184-95.
[15].Koken MH, Reynolds P, Jaspers-Dekker I, et al. Structural and functional conservation of two human homologs of the yeast DNA repair gene RAD6[J]. Proc Natl Acad Sci USA,1991,88(20):8865-9.
[16].Kim J, Guermah M, McGinty RK, et al. RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells[J]. Cell, 2009,137(3):459-71.
[17].Kim J, Hake SB, Roeder RG, et al. The human homolog of yeast BRE1 functions as a transcriptional coactivator through direct activatorinteractions[J]. Mol Cell,2005, 20(5):759-70.
[18].Zhu B, Zheng Y, Pham AD, et al. Monoubiquitination of human histone H2B:the factors involved and their roles in HOX gene regulation[J]. Mol Cell,2005, 20(4):601-11.
[19].Huen MS, Grant R, Manke I, et al. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly[J]. Cell,2007,131(5):901-14.
[20].Kolas NK, Chapman JR, Nakada S, et al. Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase[J]. Science,2007,318(5856):1637-40.
[21].Mailand N, Bekker-Jensen S, Faustrup H, et al. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins[J]. Cell,2007, 131(5):887-900.
[22].Wang B, Elledge SJ. Ubcl3/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brcal/Brcc36 complex in response to DNA damage[J]. Proc Natl Acad Sci USA,2007,104(52):20759-63.
[23].Doil C, Mailand N, Bekker-Jensen S, et al. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins[J].Cell,2009,136(3):435-46.
[24].Stewart GS, Panier S, Townsend K, et al. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage[J].Cell,. 2009 136(3):420-34.
[25]Joo HY, Zhai L, Yang C, et al. Regulation of cell cycle progression and gene expression by H2A deubiquitination[J]. Nature,2007,449(7165):1068-72.
[26].Shanbhag NM, Rafalska-Metcalf IU, Balane-Bolivar C, et al. ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks.Cell, 2010,141(6):970-81.
[27].Zhu P, Zhou W, Wang J, et al. A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation[J]. Mol Cell,2007,27(4):609-21.
[28].Nakagawa T, Kajitani T, Togo S, et al. Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di-and trimethylation[J]. Genes Dev,2008,22(1):37-49.
[29].Scheuermann JC, de Ayala Alonso AG, Oktaba K, et al. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB.Nature [J].2010, 465(7295):243-7.
[30].Henry KW, Wyce A, Lo WS, et al. Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8[J]. Genes Dev,2003,17(21):2648-63.
[31].Daniel JA, Torok MS, Sun ZW, et al. Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription[J]. J Biol Chem,2004, 279(3):1867-71.
[32].Emre NC, Ingvarsdottir K, Wyce A, et al. Maintenance of low histone ubiquitylation by Ubp10 correlates with telomere-proximal Sir2 association and gene silencing[J]. Mol Cell,2005,17(4):585-94.
[33].Buszczak M, Paterno S, Spradling AC, et al. Drosophila stem cells share a common requirement for the histone H2B ubiquitin protease scrawny [J]. Science, 2009,323(5911):248-51.
[34].van der Knaap JA, Kumar BR, Moshkin YM,et al. GMP synthetase stimulates histone H2B deubiquitylation by the epigenetic silencer USP7[J]. Mol Cell,2005, 17(5):695-707.
[35].Nicassio F, Corrado N, Vissers JH, et al.Human USP3 is a chromatin modifier required for S phase progression and genome stability[J]. Curr Biol,2007, 17(22):1972-7.
[36].Joo HY, Jones A, Yang C, et al. Regulation of histone H2A and H2B deubiquitination and Xenopus development by USP12 and USP46[J]. J Biol Chem, 2011,286(9):7190-201.
[37].Zhang XY, Pfeiffer HK, Thome AW, et al. USP22, An hSAGA subunit and potential cancer stem cell marker,reverses the polycomb-catalyzed ubiquitylation of histone H2A[J]. Cell Cycle,2008,7(11):1522-1524.
[38].Lang G, Bonnet J, Umlauf D, et al. The tightly controlled deubiquitination activity of the human SAGA complex differentially modifiesdistinct gene regulatory elements[J]. Mol Cell Biol,2011,31(18):3734-44.
[39].Dover J, Schneider J, Tawiah-Boateng MA, et al.Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6[J]. J Biol Chem,2002, 277(32):28368-71.
[40].Sun ZW, Allis CD. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast[J]. Nature,2002,418(6893):104-8.
[41].Lee JS, Shukla A, Schneider J, et al. Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by COMPASS [J]. Cell.2007, 131(6):1084-96.
[42].Blair LP, Cao J, Zou MR, et al. Epigenetic Regulation by Lysine Demethylase 5 (KDM5) Enzymes in Cancer.Cancers (Basel)[J].2011,3(1):1383-404.
[43].Xiao T, Kao CF, Krogan NJ, et al. Histone H2B ubiquitylation is associated with elongating RNA polymerase II[J]. Mol Cell Biol.2005,25(2):637-51.
[44].Zhang XY, Varthi M, Sykes SM, et al. The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activatedtranscription and cell-cycle progression[J]. Mol Cell,2008,29(1):102-11.
[45].Cao J, Yan Q. Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer[J]. Front Oncol,2012,12;2:26.
[46].Wyce A, Xiao T, Whelan KA, et al. H2B ubiquitylation acts as a barrier to Ctkl nucleosomal recruitment prior to removal by Ubp8 within a SAGA-related complex[J].Mol Cell,2007,27(2):275-88.
[47].Lee MG, Villa R, Trojer P, et al. Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination[J]. Science,2007,318(5849):447-50.
[48].Prenzel T, Begus-Nahrmann Y, Kramer F, et al. Estrogen-dependent gene transcription in human breast cancer cells relies upon proteasome-dependentmonoubiquitination of histone H2B[J]. Cancer Res,2011, 71(17):5739-53.
[49].Shema E, Tirosh I, Aylon Y, et al.The histone H2B-specific ubiquitin ligase RNF20/hBREl acts as a putative tumor suppressor through selectiveregulation of gene expression[J]. Genes Dev,2008,22(19):2664-76.
[50].Shema E, Kim J, Roeder RG,et al. RNF20 inhibits TFIIS-facilitated transcriptional elongation to suppress pro-oncogenic gene expression[J]. Mol Cell, 2011,42(4):477-88.
[51].Glinsky GV, Berezovska O, Glinskii AB. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer[J].J Clin Invest,2005,115:1503-1521.
[52].Glinsky GV. Genomic models of metastatic cancer:funtional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated Polycomb Group (PcG)protein chromatin silencing pathway[J].Cell Cycle,2006,5:1208-1216.
[53].Lin Z, Yang H, Kong Q,et al. USP22 antagonizes p53 transcriptional activation by deubiquitinating SIRT1 to suppress cell apoptosis and is required for mouse embryonic development. Mol Cell 2012; 46 (4) 484-494.
[54].Zhao Y, Lang G, Ito S, et al. A TFTC/STAGA MoDule Mediates Histone H2A and H2B Deubiquitination,Coactivates Nuclear Receptors, and Counteracts Heterochromatin Silencing[J]. Mol Cell,2008,29:92-101.
[55].Lee HJ,Kim MS, Shin JM, et al. The expression patterns of deubiquitinating enzymes,USP22and Usp22[J]. Gene ExpressionPatterns 6,2006,277-284.
[56].Satija YK, Bhardwaj A, Das S. A portrayal of E3 ubiquitin ligases and deubiquitylases in cancer[J]. Int J Cancer,2013,133(12):2759-68.
[57].Samara NL, Wolberger C. A new chapter in the transcription SAGA[J]. Curr Opin Struct Biol,2011;21(6):767-74.
[58].Liu X, Teisfai J, Martinez E, et al. C-MYC transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for transcription activation[J] J Biol Chem,2003; 278(22):20405-20412.
[59].Liu YL, Jiang SX, Yang YM, et al. USP22 acts as an oncogene by the activation of BMI-1-mediated INK4a/ARF pathway and Akt pathway[J]. Cell Biochem Biophys, 2012,62(1):229-35.
[60].Xu H, Liu YL, Yang Ym, et al. Knock-down of ubiquitin-specific protease 22 by micro-RNA interference inhibits colorectal cancer growth[J]. International Journal of Colorectal Disease,2012,27:21-30.
[61].Atanassov BS, Dent SYR. USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1[J]. Embo Reports,2011,12:924-930.
[62].Lv L, Xiao XY, Gu ZH et al. Silencing USP22 by asymmetric structure of interfering RNA inhibits proliferation and induces cell cycle arrest in bladder cancer cells[J]. Mol Cell Biochem,2011,346(1-2):11-21.
[63].Sridharan R1, Tchieu J, Mason MJ, et al. Role of the murine reprogramming factors in the induction of pluripotency[J]. Cell,2009,136(2):364-77.
[64].Sussman RT, Stanek TJ, Esteso P, et al. The epigenetic modifier ubiquitin-specific protease 22 (USP22) regulates embryonic stem cell differentiation via transcriptional repression of sex-determining region Y-box 2 (SOX2)[J]. J Biol Chem,2013,288(33):24234-46.
[65].Dai W, Yao Y, Zhou Q, et al. Ubiquitin-specific peptidase 22, a histone deubiquitinating enzyme, is a novel poor prognostic factor for salivary adenoid cystic carcinoma[J]. PLoS One,2014,9(1):e87148.
[66].Yang M, Liu YD, Wang YY, et al. Ubiquitin-specific protease 22:a novel molecular biomarker in cervical cancer prognosis and therapeutics [J]. Tumour Biol, 2014,35(2):929-3.
[67].Piao S, Ma J, Wang W, et al. Increased expression of USP22 is associated with disease progression and patient prognosis of salivary duct carcinoma[J]. Oral Oncol, 2013,49(8):796-801.
[68].Wang H, Li YP, Chen JH, et al. Prognostic significance of USP22 as an oncogene in papillary thyroid carcinoma[J]. Tumour Biol,2013,34(3):1635-9.
[69].Ning J, Zhang J, Liu W, et al.Overexpression of ubiquitin-specific protease 22 predicts poor survival in patients with early-stage non-small cell lung cancer [J]. Eur J Histochem,2012,56(4):e46.
[70].Piao S, Liu Y, Hu J, et al. USP22 is useful as a novel molecular marker for predicting disease progression and patient prognosis of oral squamous cell carcinoma[J]. PLoS One,2012,7(8):e42540.
[71].Li J, Wang Z, Li Y, et al. USP22 nuclear expression is significantly associated with progression and unfavorable clinical outcome in human esophageal squamous cell carcinoma[J]. J Cancer Res Clin Oncol,2012,138(8):1291-7.
[72].Liu YL, Yang YM, Xu H, et al. Aberrant expression of USP22 is associated with liver metastasis and poor prognosis of colorectal cancer [J]. J Sur Oncol,2011, 103(3):283-289.
[73].Zhang Y, Yao L, Zhang X, et al. Elevated expression of USP22 in correlation with poor prognosis in patients with invasive breast cancer [J]. J Cancer Res Clin Onco,2011,137(8):1245-53.
[74].Yang DD, Cui BB, Sun LY, et al. The co-expression of USP22 and BMI-1 may promote cancer progression and predict therapy failure in gastric carcinoma.Cell Biochem Biophys,2011,61(3):703-10.
[75].Luo Y, Zeng FQ, Gu ZH, et al. Quantitative analysis of the putative cancer stem cell marker USP22 mRNA in the transitional cell carcinoma of the bladder and the relationship between USP22 and the grading of tumor[J]. J Clin Urol,2009, 24(2):140-144.
[76].Liu Y, Yang Y, Xu H, et al. Implication of USP22 in the regulation of BMI-1, c-Myc, p16INK4a, p14ARF, and cyclin D2 expression in primary colorectal carcinomas[J]. Diagn Mol Patho,2010,19(4):194-200.
[77].Schrecengost RS, Dean JL, Goodwin JF, et al. USP22 regulates oncogenic signaling pathways to drive lethal cancer progression[J]. Cancer Res,2014, 74(1):272-86.
[78].Daniel J A, Grant PA. Multi-tasking on chromatin with the SAGA coactivator complexes [J]. Mutat Res,2007,618(122):135-148.
[79].Liu YL, Yang YM, Xu H, et al.Increased expression of ubiquitin-specific protease 22 can promote cancer progression and predict therapy failure in human colorectal cancer[J]. J Gastroenterol Hepatol,2010,25(11):1800-5
[80].Xiong JJ, Gan LJ, Lin L, et al. Construction and identification of eukaryotic expression plasmid expressing siRNA targeting USP22 gene[J]. Sichuan Da Xue Xue Bao Yi Xue Ban,2011,42(2):166-9.
[81].Ling SB, Sun DG, Tang B, et al. Knock-down of USP22 by small interfering RNA interference inhibits HepG2 cell proliferation and induces cell cycle arrest[J]. Cell Mol Biol (Noisy-le-grand),2012,58:1803-8.
[82].Hu J, Liu YL, Piao SL, et al. Expression patterns of USP22 and potential targets BMI-1, PTEN, p-AKT in non-small-cell lung cancer [J]. Lung Cancer,2012, 77(3):593-9.
[83].Liu S, Dontu G, Mantle ID, et al. Hedgehog signaling and BMI-1 regulate self-re newal of normal and malignant human mammary stem cells[J]. Cancer Res, 2006,66(12):6063-6071.
[84].A1-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells[J].Oncogene, 2004,23(43):7274-7282.
[85].Davie JR, Murphy LC. Level of ubiquitinated histone H2B in chromatin is coupled to ongoing transcription[J]. Biochemistry,1990,29(20):4752-7
[86].Schwartz AL, Trausch JS, Ciechanover A, et al.Immunoelectron microscopic localization of the ubiquitin-activating enzyme El in HepG2 cells[J]. Proc Natl Acad Sci USA,1992,89(12):5542-6.
[87].Ciechanover A, Orian A, Schwartz AL, et al.The ubiquitin-mediated proteolytic pathway:mode of action and clinical implications[J]. J Cell Biochem Suppl,2000, 34:40-51.
[88].Wilkinson KD. Ubiquitin-dependent signaling:the role of ubiquitination in the response of cells to their environment[J]. J Nutr,1999,129(11):1933-6.
[89].Mimnaugh EG, Bonvini P, Neckers L, et al. The measurement of ubiquitin and ubiquitinated proteins[J]. Electrophoresis,1999,20(2):418-28.
[90].Weissman AM. Regulating protein degradation by ubiquitination[J].Immunol Today,1997,18(4):189-98.
[91].Luscher B, Vervoorts J. Regulation of gene transcription by the oncoprotein MYC[J].Gene,2012,;494(2):145-60.
[92].Muller J, Eilers M. Ubiquitination of Myc:proteasomal degradation and beyond[J]. Ernst Schering Found Symp Proc,2008(1):99-113.
[93].Sun Y, Li H. Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase[J]. Protein Cell,2013,4(2):103-16.
[94].Jariel-Encontre I, Bossis G, Piechaczyk M.Ubiquitin-independent degradation of proteins by the proteasome[J]. Biochim Biophys Acta,2008,1786(2):153-77.
[95].Ichihara A, Tanaka K. Roles of proteasomes in cell growth[J]. Mol Biol Rep, 1995,21(1):49-52.
[96].Ingley E.Src family kinases:regulation of their activities, levels and identification of new pathways[J]. Biochim Biophys Acta,2008,1784(1):56-65.
[97].Ben-Neriah Y.Regulatory functions of ubiquitination in the immune system[J]. Nat Immunol,2002,3(1):20-6.
[98].Moutoussamy S, Kelly PA, Finidori J, et al. Growth-hormone-receptor and cytokine-receptor-family signaling[J]. Eur J Biochem,1998,255(1):1-11.
[99].Nguyen LK, Kolch W, Kholodenko BN. When ubiquitination meets phosphorylation:a systems biology perspective of EGFR/MAPK signalling [J]. Cell Commun Signal,2013,11:52.
[100].Xiu X, Lu ZM.Ubiquitination-mediated degradation of epidermal growth factor receptor[J]. Zhong guo Yi Xue Ke Xue Yuan Xue Bao,2005,27(1):120-7.
[101].Stamos JL, Weis WI. The (3-catenin destruction complex[J]. Cold Spring Harb PerspectBiol,2013,5(1):a007898.
[102].Kikuchi A, Kishida S. Abnormal regulation of beta-catenin degradation through ubiquitination as a mechanism of carcinogenesis[J]. Tanpakushitsu Kakusan Koso, 2006,51(10 Suppl):1271-6.
[103].Kikuchi A, Kishida S, Yamamoto H. Regulation of Wnt signaling by protein-protein interaction and post-translational modifications[J]. Exp Mol Med, 2006,38(1):1-10.
[104].Fuchs SY.The role of ubiquitin-proteasome pathway in oncogenic signaling[J]. Cancer Biol Ther,2002,1(4):337-41.
[105].Mohapatra B, Ahmad G, Nadeau S, et al. Protein tyrosine kinase regulation by ubiquitination:critical roles of Cbl-family ubiquitin ligases[J]. Biochim Biophys Acta, 2013,1833(1):122-39.
[106].Severe N, Marie P. Implication of the ubiquitin ligase c-Cbl in bone formation and tumorigenesis[J].Med Sci (Paris),2012,28(11):970-5.
[107].Gay DL, Ramon H, Oliver PM. Cbl-and Nedd4-family ubiquitin ligases: balancing tolerance and immunity[J]. Immunol Res,2008,42(1-3):51-64.
[108].Ingley E.Src family kinases:regulation of their activities, levels and identification of new pathways[J]. Biochim Biophys Acta.2008,1784(1):56-65.
[109].Venuprasad K.Cbl-b and itch:key regulators of peripheral T-cell tolerance [J]. Cancer Res,2010,70(8):3009-12.
[110].Ardley HC, Robinson PA.E3 ubiquitin ligases[J]. Essays Biochem,2005, 41:15-30.
[111].Lu Z, Hunter T. Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors [J]. Cell Cycle,2010,9(12):2342-52.
[112].Kotoshiba S, Nakayama K.The degradation of p27 and cancer[J]. Nihon Rinsho. 2005,63(11):2047-56.
[113].Stewart D, Ghosh A, Matlashewski G. Involvement of nuclear export in human papillomavirus type 18 E6-mediated ubiquitination and degradation of p53[J]. J Virol, 2005,79(14):8773-83.
[114].Gewin L, Myers H, Kiyono T, et al. Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex[J]. Genes Dev,2004,18(18):2269-82.
[115].Ma J, Martin JD, Xue Y, et al. C-terminal region of USP7/HAUSP is critical for deubiquitination activity and contains a second mdm2/p53 binding site[J]. Arch Biochem Biophys,2010,503(2):207-12.
[116].Song MS, Song SJ, Kim SY, et al. The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex[J]. EMBO J,2008,27(13):1863-74.
[117].Becker K, Marchenko ND, Palacios G. A role of HAUSP in tumor suppression in a human colon carcinoma xenograft model[J]. Cell Cycle,2008,7(9):1205-13.
[118].Brazhnik P, Kohn KW. HAUSP-regulated switch from auto-to p53 ubiquitination by Mdm2 (in silico discovery)[J]. Math Biosci,2007,210(1):60-77.
[2].Gralnek IM, Siersema PD, Halpern Z, et al. Standard forward-viewing colonoscopy versus full-spectrum endoscopy:an international, multicentre, randomised, tandem colonoscopy trial[J]. Lancet Oncol,2014,15(3):353-60.
[3].Glinsky GV, Berezovska O, Glinskii AB, et al. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer[J]. J Clin Invest,2005,115(6):1503-1521.
[4].Glinsky GV. Genomic models of metastatic cancer:funtional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated Polycomb Group (PcG)protein chromatin silencing pathway[J]. Cell Cycle,2006,5(11): 1208-1216.
[5].Lee HJ,Kim MS, Shin JM, et al. The expression patterns of deubiquitinating enzymes,USP22and Usp22[J]. Gene ExpressionPatterns 6,2006,6(3):277-284.
[6].Xiao YZ, Harla KP, Alan WT, et al. USP22, An hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquity lation of histone H2A[J]. Cell Cycle,2008,7(11):1522-1524.
[7].Zhang X-Y, Varthi M, Sykes SM, et al. The Putative Cancer Stem Cell Marker USP22 Is a Subunit of the Human SAGA Complex Required for Activated Transcription and Cell-Cycle Progression[J]. Mol Cell,2008,29(1):102-111.
[8].Liu YL, Jiang SX, Yang YM, et al.USP22 Acts as an Oncogene by the Activation of BMI-1-Mediated INK4a/ARF Pathway and Akt Pathway[J]. Cell Biochem Bio-phys,2012,62(1):229-35.
[9].Xu H, Liu YL, Yang Ym, et al. Knock-down of ubiquitin-specific protease 22 by micro-RNA interference inhibits colorectal cancer growth[J]. International Journal of Colorectal Disease,2012,27(1):21-30.
[10].Guney, I., Wu, S., and Sedivy, J.M. Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and pl6(INK4a)[J]. Proc Natl Acad Sci USA,2006,103(10):3645-3650.
[11].Kim JH, Yoon SY, Kim CN, et al. The Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlateswith the reduced p16 INK4a/p14ARF protein[J]. Cancer Lett,2004,203 (2):217-224.
[12].Sridharan R, Tchieu J, Mason MJ, et al. Role of the murine reprogramming factors in the induction of pluripotency[J]. Cell,2009,136(2):364-77.
[13].Sussman RT, Stanek TJ, Esteso P, et al. The epigenetic modifier ubiquitin-specific protease 22 (USP22) regulates embryonic stem cell differentiation via transcriptional repression of sex-determining region Y-box 2 (SOX2)[J]. J Biol Chem,2013,288(33):24234-46.
[14].Lin Z, Yang H, Kong Q, et al.USP22 antagonizes p53 transcriptional activation by deubiquitinating Sirtl to suppress cell apoptosis and isrequired for mouse embryonic development[J], Mol Cell.2012,46(4):484-94.
[15].Rahman S, Islam R. Mammalian Sirtl:insights on its biological functions[J]. Cell Communication and Signaling,2011,9:11.
[16].Hajji N, Wallenborg K, Vlachos P, et al. Opposing effects of hMOF and SIRT1 on H4K16 acetylation and the sensitivity to the topoisomerase II inhibitor etoposide[J]. Oncogene,2010,29(15):2192-204.
[17].Jung-Hynes B, Ahmad N. Role of p53 in the anti-proliferative effects of Sirtl inhibition in prostate cancer cells[J]. Cell Cycle,2009,8(10):1478-1483.
[18]Dai JM, Wang ZY, Sun DC, et al. SIRT1 interacts with p73 and suppresses 73-dependent transcriptional activit[J]. J Cell Physiol,2007,210(1):161-166.
[19].Sedding DG. FoxO transcription factors in oxidative stress response and ageing-a new fork on the way to longevity? [J]. Biol Chem,2008, 389(3):279-283.
[20].Fu M, Liu M, S auve AA, et al. Hormonal control of androgen recept or function through SIRT1[J]. Mol Cell Biol,2006,26(21):8122-8135.
[21].Wang C, Chen L, Hou X, et al. Interactions between E2F 1 and SirTl regulate apoptotic response to DNA damage[J]. Nat Cell Biol,2006,8(9):1025-1031.
[22].Ghosh HS, McBurney M, Robbins PD. SIRT1 negatively regulates the mammalian target of rapamycin[J]. PLoS One,2010,5(2):e9199.
[23].Yuan J, Minter-Dykhouse K, Lou Z. A c-Myc-SIRT1 feedback loop regulates cell growth and transformation[J]. J Cell Biol.2009 Apr 20;185(2):203-11.
[24].Firestein R, Blander G, Michan S,et al. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth[J]. PLoS One.2008,3(4):e2020.
[25].Lim JH, Lee YM, Chun YS, et al. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor lalpha[J]. Mol Cell.2010, 38(6):864-78.
[26].Blander G, Guarente L. The Sir2 family of protein deacetylases[J]. Annu Rev Biochem,2004,73(2):417-435.
[27].Tao Liu, Pei Y. Liu, Glenn M. Marshall. The Critical Role of the Class III Histone Deacetylase SIRT1[J]..Cancer Res,2009,69 (5):1702-1705.
[28].Bradbury CA, Khanim FL, Hayden R, et al. Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors[J]. Leukemia,2005,19(10):1751-1759.
[29].Liu G, Yuan X, Zeng Z, et al. Analysis of gene expression and chemoresistance of CD133+cancer stem cells in glioblastoma[J]. Mol Cancer,2006,5:67.
[30].Huffman DM, Grizzle WE, Bamman MM, et al. SIRT1 is significantly elevated in mouse and human prostate cancer[J].Cancer Res,2007,67(14):6612-6618.
[31].Stunkel W, Peh BK, Tan YC,et al. Function of the SIRT1 protein deacetylase in cancer[J]. Biotechnol J,2007,2(11):1360-1368.
[32].Deng CX. SIRT1, Is It a Tumor Promoter or Tumor Suppressor?[J]. Int J Biol Sci,2009,5(2):147-152.
[33].Wang RH, Sengupta K, Li C, et al. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice[J]. Cancer Cell,2008, 14(4):312-323.
[34].Armour SM, Bennett EJ, Braun CR, et al. A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex[J]. Mol Cell Biol,2013,33(8):1487-502.
[35].Zhang J, Lee SM, Shannon S, et al. The type III histone deacetylase SIRT1 is essential for maintenance of T cell tolerance in mice[J]. J Clin Invest,2009, 119:3048-3058.
[36].Sestito R, Madonna S, Scarponi C, et al. STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a directinhibition of STAT3 acetylation[J]. FASEB J 2011,25(3):916-27.
[37].Ailfrey VG, Faulkner K, Mirsky AE. Acetrlation and Methylation of Histones and Their Possible Role in the Regulation of Rna Synthesis[J]. Proc Natl Acad Sci, 1964,51:786-794.
[38].Vidali G, Boffa LC, Bradbury EM, et al. Butyrate suppression of histone deacetyrlation leads to accumulation of multiacetylated forms of histones H3 and H4 and increased DNase I sensitivity of the associated DNA sequences [J]. Proe Natl Aead Sci,1978,75:2239-2243.
[39].Hebbes TR, Thorne AW, Crane-Robinson C. A direct link between core histone acetyrlation and transcriptionally active chromatin[J]. EMBO J,1988,7:1395-1402.
[40].Lee DY, Hayes JJ, Pruss D, et al. A positive role for histone acetylation in transcription factor access to nucleosomal DNA [J]. Cell,1993,72:73-84.
[41].Vettese-Dadey M, Grant PA, Hebbes TR, et al. Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro[J]. EMBO J,1996,15:2508-2518.
[42].Yuan ZL, Guan YJ, Chatterjee D, et al. Stat3 dimerization regulated by reversible acetylation of a single lysine residue [J]. Science,2005,307:269-273
[43].O'Shea JJ, Kanno Y, Chen X, et al. Cell signaling. Stat acetylation-a key facet of cytokine signaling?[J]. Science,2005,307:217-218.
[44].Varinou L, Ramsauer K, Karaghiosoff M, et al. Phosphorylation of the Statl transactivation domain is required for full-fledged IFN-gamma-dependent innate immunity[J]. Immunity,2003,19:793-802.
[45].Levy DE, Darnell JE, Jr. Stats:transcriptional control and biological impact[J]. Nat Rev Mol Cell Biol,2002,3:651-662. [46].Shuai K. Serine phosphorylation:arming Stati against infection[J]. Immunity, 2003,19:771-772
[47].Alvarez JV, Frank DA. Genome-wide analysis of STAT3 target genes: elucidating the mechanism of STAT-mediated oncogenesis[J]. Cancer Biol Ther 2004, 3(11):1045-50.
[48].Bugno M, Graeve L, Gatsios P, et al. Identification of the interleukin-6/oncostatin M response element in the rat tissue inhibitor of metalloproteinases-1 (TIMP-1) promoter[J]. Nuc Acids Res,1995,23:5041-5047.
[49].Cheng GZ, Zhang WZ, Sun M, Wang Q, Coppola D, et al. Twist is transcriptionally induced by activation of STAT3 and mediates STAT3 oncogenic function[J]. J Biol Chem 2008,283:14665-14673.
[50].Niu G, Briggs J, Deng J, et al. Signal transducer and activator of transcription 3 is required for hypoxia-inducible factor-1 alpha RNA expression in both tumor cells and tumor-associated myeloid cells[J]. Mol Cancer Res,2008,6:1099-105.
[51].Niu G, Wright KL, Huang M, et al. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis[J]. Oncogene,2002,21:2000-8.
[52].Zhang M, Liu Y, Feng H, et al. CD133 affects the invasive ability of HCT116 cells by regulating TIMP-2[J]. Am J Pathol,2013,182(2):565-76.
[53].Kajita M, Itoh Y, Chiba T, et al. Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration[J]. J Cell Biol,2001,153(5):893-904.
[54].Spessotto P, Rossi FM, Degan M.et al. Hyaluronan-CD44 interaction hampers migration of osteoclast-like cells by down-regulating MMP-9[J]. J CellBiol,2002, Biol.158(6):1133-44.
[55].Huth JR, Yu LP, Collins I, et al. NMR-Driven Discovery of Benzoylanthranilic Acid Inhibitors of Far Upstream Element Binding Protein Binding to the Human Oncogene c-myc Promoter[J]. J Med Chem,2004,47(20):4851-7.
[56].Atanassov BS, Dent SY. USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1[J]. Embo Reports,2011,12:924-930.
[57].Pankratz SL, Tan EY, Fine Y,et al. Insulin receptor substrate-2 regulates aerobic glycolysis in mouse mammary tumor cells via glucose transporter 1[J], J Biol Chem, 2009,284(4):2031-7.
[58].Liu P, Wilson MJ. miR-520c and miR-373 upregulate MMP9 expression by targeting mTOR and SIRT1, and activate theRas/Raf/MEK/Erk signaling pathway and NF-kB factor in human fibrosarcoma cells[J]. J Cell Physiol,2012,227(2):867-76.
[59].Liu Y, Yang Y, Xu H,et al. Implication of USP22 in the regulation of BMI-1, c-Myc, p16INK4a, p14ARF, and cyclin D2 expression in primary colorectal carcinomas[J]. Diagn Mol Patho,2010,19(4):194-200.
[60].Liu YL, Yang YM, Xu H, et al.Increased expression of ubiquitin-specific protease 22 can promote cancer progression and predict therapy failure in human colorectal cancer[J]. J Gastroenterol Hepatol.2010,25(11):1800-5.
[61].Liu YL, Yang YM, Xu H, et al. Aberrant expression of USP22 is associated with liver metastasis and poor prognosis of colorectal cancer [J]. J Sur Oncol,2011, 103(3):283-289.
[62].Li ZW, Liu YQ:Progress of targeted therapy related to K-ras mutation. Zhong Hua Bing Li Xue Za Zhi 2012; 41(1):59-61.
[63].Ohbayashi N, Ikeda O, Taira N, et al. LIF-and IL-6-induced acetylation of STAT3 at Lys-685 through PI3K/Akt activation[J]. Biol Pharm Bull,2007, 30(10):1860-4.
[64].Folkman J, Shing Y.Angiogenesis[J]. J Biol Chem,1992,267(16):10931-4.
[65].Takahashi Y, Kitadai Y, Bucana CD, et al. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer[J]. Cancer Res,1995,55(18):3964-8.
[66].Ma XT, Wang S, Ye YJ, et al. Constitutive activation of Stat3 signaling pathway in human colorectal carcinoma[J].World J Gastroenterol,2004,10(11):1569-73.
[67].Wei X, Wang G, Li W, et al. Activation of the JAK-STAT3 pathway is associated with the growth of colorectal carcinoma cells[J]. Oncol Rep,2014,31(1):335-41.
[68].Siveen KS1, Sikka S2, Surana R, et al. Targeting the STAT3 signaling pathway in cancer:Role of synthetic and natural inhibitors [J]. Biochim Biophys Acta,2014, 1845(2):136-154.
[69].Pratt SL, Ogle CK, Mao JX, et al.Interleukin-6 signal transduction in human intestinal epithelial cells [J].Shock,2000,13(6):435-40.
[70].Karpf AR, Peterson PW, Rawlins JT, et al.Inhibition of DNA methyltransferase stimulates the expression of signal transducer and activator oftranscription 1,2, and 3 genes in colon tumor cells[J]. Proc Natl Acad Sci USA,1999,96(24):14007-12.
[72].Orlovsky K, Theodor L, Malovani H, et al/Gamma interferon down-regulates Fer and induces its association with inactive Stat3 in coloncarcinoma cells [J]. Oncogene. 2002,21(32):4997-5001.
[73].Ma X, Wang S, Du R, et al.Stat3 signal transduction pathway orchestrates G1 to S cell cycle transition in colon cancer cells[J].Beijing Da Xue Xue Bao,2003, 35(l):50-3.
[74].Ma XT, Wang S, Ye YJ,et al.Relationship of Stat3 and its target gene products with malignancy in human colorectal carcinoma[J]. Ai Zheng,2003,22(11):1135-9.
[75].Herbeuval JP, Lelievre E, Lambert C, et al.Recruitment of STAT3 for production of IL-10 by colon carcinoma cells induced by macrophage-derived IL-6[J]. J Immunol, 2004,172(7):4630-6.
[76].Corvinus FM, Orth C, Moriggl R, et al.Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth[J]. Neoplasia. 2005,7(6):545-55.
[77].Atreya R, Neurath MF. Involvement of IL-6 in the pathogenesis of inflammatory bowel disease and colon cancer[J]. Clin Rev Allergy Immunol,2005,28(3):187-96.
[78].Lin Q, Lai R, Chirieac LR, Li C, et al. Constitutive activation of JAK3/STAT3 in colon carcinoma tumors and cell lines:inhibition of JAK3/STAT3 signaling induces apoptosis and cell cycle arrest of colon carcinoma cells[J]. Am J Pathol.2005 167(4):969-80.
[79].Becker C, Fantini MC, Schramm C, et al.TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling[J]. Immunity,2004, 21(4):491-501.
[80].Tomida M, Ohtake H, Yokota T, et al.Stat3 up-regulates expression of nicotinami-de N-methyltransferase in human cancer cells[J]. J Cancer Res Clin Oncol. 2008,134(5):551-9.
[81].Tsareva SA, Moriggl R, Corvinus FM, et al.Signal transducer and activator of transcription 3 activation promotes invasive growth of coloncarcinomas through matrix metalloproteinase induction[J]. Neoplasia.2007,9(4):279-91.
[82].Valdes-Mora F, Gomez del Pulgar T, Bandres E, et al. TWIST1 overexpression is associated with nodal invasion and male sex in primary colorectalcancer[J]. Ann Surg Oncol,2009,16(1):78-87
[83].Gavert N, Vivanti A, Hazin J, et al. L1-mediated colon cancer cell metastasis does not require changes in EMT and cancer stem cell markers[J]. Mol Cancer Res, 2011,9(1):14-24.
[84].Qi L, Sun B, Liu Z, et al. Dickkopf-1 inhibits epithelial-mesenchymal transition of colon cancer cells and contributes to colon cancer suppression[J]. Cancer Sci,2012, 103(4):828-35
[85].Lv Q, Wang W, Xue J, et al. DEDD interacts with PI3KC3 to activate autophagy and attenuate epithelial-mesenchymal transition in human breast cancer[J]. Cancer Res,2012,72(13):3238-50
[86].Pawelek JM, Chakraborty AK. The cancer cell--leukocyte fusion theory of metastasis[J]. Adv Cancer Res,2008,101:397-444.
[87].Celesti G, Di Caro G, Bianchi P, et al. Presence of Twistl-positive neoplastic cells in the stroma of chromosome-unstable colorectal tumors [J]. Gastroenterology, 2013,145(3):647-57
[88].Singh N, Liu G, Chakrabarty S. Isolation and characterization of calcium sensing receptor null cells:a highly malignant and drug resistant phenotype of colon cancer[J].Int J Cancer,2013,132(9):1996-2005
[89].Pelaez-Garcia A, Barderas R, Torres S, et al. PFGFR4 role in epithelial-mesenchymal transition and its therapeutic value in colorectal cancer [J]. PLoS One.2013,8(5):e63695.
[90].Meng XN, Jin Y, Yu Y, et al.Characterisation of fibronectin-mediated FAK signalling pathways in lung cancer cell migration andinvasion[J]. Br J Cancer.2009, 101(2):327-34.
[91].Loesch M, Zhi HY, Hou SW, et al.p38gamma MAPK cooperates with c-Jun in trans-activating matrix metalloproteinase 9[J]. J Biol Chem.2010,285(20):15149-58.
[92].Park KS, Kim SJ, Kim KH, et al.Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer[J].J Gastroenterol Hepatol,2011, 26(2):391-7
[93].Li D, Sun X, Yan D, Piwi12 modulates the proliferation and metastasis of colon cancer via regulation of matrix metallopeptidase 9 transcriptional activity [J].Exp Biol Med (Maywood),2012,237(10):1231-40.
[94].Park KS, Kim SJ, Kim KH, et al.Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer[J]. J Gastroenterol Hepatol,2011, 26(2):391-7.
[1].Sun, ZW, Allis CD. The language of covalent histone modications[J]. Nature,2002, 403(6765):41-45.
[2].Goldknopf I, Taylor CW, Baum RM et al. Isolation and characterization of proteinA 24, a "histone-like"non-histonechromosomal protein[J]. J Biol Chem,1975, 250(18):7182-7187
[3].Robzyk K, Recht J, Osley MA. Rad6-dependentubiquitination of histone H2B in yeast[J]. Science,2000,287(5452):501-504.
[4].Matsui SI, Seon BK, Sandberg AA et al. Disappearanceof a structural chromatin proteinA 24 in mitosis implications for molecular basis of chromatincondensatio[J]. Proc Natl Acad Sci,1979,76(12):6386-6390.
[5].Wang H.,Wang L, Erdjument-Bromage H, et al. Role of histone H2A ubiquitination in Polycomb silencing[J]. Nature,2004,431(7010):873-878.
[6].Cao R.,Tsukada Y, Zhang Y, et al. Role of Bmi-1 and RinglA in H2A ubiquitylation and Hoxgene silencing[J]. Mol Cell,2005,20(6):845-854.
[7].Buchwald G, van de rStoop P, Weichenrieder O,et al. Structure and E3-ligase activity of the ring-ring complex of polycomb proteins Bmil and Ringlb[J]. EMBO J, 2006,25(11):2465-2474.
[8].Chen A, Kleiman FE, Manley JL, et al. Autoubiquitination of the BRCA1* BARD1 RING ubiquitin ligase[J]. J Biol Chem,2002,277(24):22085-22092.
[9].de Napoles M, Mermoud JE, Wakao R, et al. Polycombgroup proteins Ring1 A/Blink ubiquitylation of histone H2A to heritable gene silencing and X inactivatio[J]. Dev Cell,2004,17(5):663-676.
[10].Stock JK, Giadrossi S, Casanova M et al.Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase Ⅱ at bivalent genes in mouse ES cells [J]. Nat Cell Biol,2007,9(12):1428-35.
[11].Robzyk K, RechtJ, Osley MA. Rad6-dependentubiquitination of histone H2B in yeast[J].Science,2000,287(5452):501-504.
[12].Hwang WW, Venkatasubrahmanyam S, Ianculescu AG, et al. A conserved RING finger protein required for histone H2B monoubiquitination and cell size contro[J]. Mol Cell,2003,11(1):261-6.
[13].Wood A, Krogan NJ, Dover J,et al. Brel, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter[J]. Mol Cell,2003, 11(1):267-74.
[14].Kao CF, Hillyer C, Tsukuda T, et al. Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B[J]. Genes Dev,2004,18(2):184-95.
[15].Koken MH, Reynolds P, Jaspers-Dekker I, et al. Structural and functional conservation of two human homologs of the yeast DNA repair gene RAD6[J]. Proc Natl Acad Sci USA,1991,88(20):8865-9.
[16].Kim J, Guermah M, McGinty RK, et al. RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells[J]. Cell, 2009,137(3):459-71.
[17].Kim J, Hake SB, Roeder RG, et al. The human homolog of yeast BRE1 functions as a transcriptional coactivator through direct activatorinteractions[J]. Mol Cell,2005, 20(5):759-70.
[18].Zhu B, Zheng Y, Pham AD, et al. Monoubiquitination of human histone H2B:the factors involved and their roles in HOX gene regulation[J]. Mol Cell,2005, 20(4):601-11.
[19].Huen MS, Grant R, Manke I, et al. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly[J]. Cell,2007,131(5):901-14.
[20].Kolas NK, Chapman JR, Nakada S, et al. Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase[J]. Science,2007,318(5856):1637-40.
[21].Mailand N, Bekker-Jensen S, Faustrup H, et al. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins[J]. Cell,2007, 131(5):887-900.
[22].Wang B, Elledge SJ. Ubcl3/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brcal/Brcc36 complex in response to DNA damage[J]. Proc Natl Acad Sci USA,2007,104(52):20759-63.
[23].Doil C, Mailand N, Bekker-Jensen S, et al. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins[J].Cell,2009,136(3):435-46.
[24].Stewart GS, Panier S, Townsend K, et al. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage[J].Cell,. 2009 136(3):420-34.
[25]Joo HY, Zhai L, Yang C, et al. Regulation of cell cycle progression and gene expression by H2A deubiquitination[J]. Nature,2007,449(7165):1068-72.
[26].Shanbhag NM, Rafalska-Metcalf IU, Balane-Bolivar C, et al. ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks.Cell, 2010,141(6):970-81.
[27].Zhu P, Zhou W, Wang J, et al. A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation[J]. Mol Cell,2007,27(4):609-21.
[28].Nakagawa T, Kajitani T, Togo S, et al. Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di-and trimethylation[J]. Genes Dev,2008,22(1):37-49.
[29].Scheuermann JC, de Ayala Alonso AG, Oktaba K, et al. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB.Nature [J].2010, 465(7295):243-7.
[30].Henry KW, Wyce A, Lo WS, et al. Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8[J]. Genes Dev,2003,17(21):2648-63.
[31].Daniel JA, Torok MS, Sun ZW, et al. Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription[J]. J Biol Chem,2004, 279(3):1867-71.
[32].Emre NC, Ingvarsdottir K, Wyce A, et al. Maintenance of low histone ubiquitylation by Ubp10 correlates with telomere-proximal Sir2 association and gene silencing[J]. Mol Cell,2005,17(4):585-94.
[33].Buszczak M, Paterno S, Spradling AC, et al. Drosophila stem cells share a common requirement for the histone H2B ubiquitin protease scrawny [J]. Science, 2009,323(5911):248-51.
[34].van der Knaap JA, Kumar BR, Moshkin YM,et al. GMP synthetase stimulates histone H2B deubiquitylation by the epigenetic silencer USP7[J]. Mol Cell,2005, 17(5):695-707.
[35].Nicassio F, Corrado N, Vissers JH, et al.Human USP3 is a chromatin modifier required for S phase progression and genome stability[J]. Curr Biol,2007, 17(22):1972-7.
[36].Joo HY, Jones A, Yang C, et al. Regulation of histone H2A and H2B deubiquitination and Xenopus development by USP12 and USP46[J]. J Biol Chem, 2011,286(9):7190-201.
[37].Zhang XY, Pfeiffer HK, Thome AW, et al. USP22, An hSAGA subunit and potential cancer stem cell marker,reverses the polycomb-catalyzed ubiquitylation of histone H2A[J]. Cell Cycle,2008,7(11):1522-1524.
[38].Lang G, Bonnet J, Umlauf D, et al. The tightly controlled deubiquitination activity of the human SAGA complex differentially modifiesdistinct gene regulatory elements[J]. Mol Cell Biol,2011,31(18):3734-44.
[39].Dover J, Schneider J, Tawiah-Boateng MA, et al.Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6[J]. J Biol Chem,2002, 277(32):28368-71.
[40].Sun ZW, Allis CD. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast[J]. Nature,2002,418(6893):104-8.
[41].Lee JS, Shukla A, Schneider J, et al. Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by COMPASS [J]. Cell.2007, 131(6):1084-96.
[42].Blair LP, Cao J, Zou MR, et al. Epigenetic Regulation by Lysine Demethylase 5 (KDM5) Enzymes in Cancer.Cancers (Basel)[J].2011,3(1):1383-404.
[43].Xiao T, Kao CF, Krogan NJ, et al. Histone H2B ubiquitylation is associated with elongating RNA polymerase II[J]. Mol Cell Biol.2005,25(2):637-51.
[44].Zhang XY, Varthi M, Sykes SM, et al. The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activatedtranscription and cell-cycle progression[J]. Mol Cell,2008,29(1):102-11.
[45].Cao J, Yan Q. Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer[J]. Front Oncol,2012,12;2:26.
[46].Wyce A, Xiao T, Whelan KA, et al. H2B ubiquitylation acts as a barrier to Ctkl nucleosomal recruitment prior to removal by Ubp8 within a SAGA-related complex[J].Mol Cell,2007,27(2):275-88.
[47].Lee MG, Villa R, Trojer P, et al. Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination[J]. Science,2007,318(5849):447-50.
[48].Prenzel T, Begus-Nahrmann Y, Kramer F, et al. Estrogen-dependent gene transcription in human breast cancer cells relies upon proteasome-dependentmonoubiquitination of histone H2B[J]. Cancer Res,2011, 71(17):5739-53.
[49].Shema E, Tirosh I, Aylon Y, et al.The histone H2B-specific ubiquitin ligase RNF20/hBREl acts as a putative tumor suppressor through selectiveregulation of gene expression[J]. Genes Dev,2008,22(19):2664-76.
[50].Shema E, Kim J, Roeder RG,et al. RNF20 inhibits TFIIS-facilitated transcriptional elongation to suppress pro-oncogenic gene expression[J]. Mol Cell, 2011,42(4):477-88.
[51].Glinsky GV, Berezovska O, Glinskii AB. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer[J].J Clin Invest,2005,115:1503-1521.
[52].Glinsky GV. Genomic models of metastatic cancer:funtional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated Polycomb Group (PcG)protein chromatin silencing pathway[J].Cell Cycle,2006,5:1208-1216.
[53].Lin Z, Yang H, Kong Q,et al. USP22 antagonizes p53 transcriptional activation by deubiquitinating SIRT1 to suppress cell apoptosis and is required for mouse embryonic development. Mol Cell 2012; 46 (4) 484-494.
[54].Zhao Y, Lang G, Ito S, et al. A TFTC/STAGA MoDule Mediates Histone H2A and H2B Deubiquitination,Coactivates Nuclear Receptors, and Counteracts Heterochromatin Silencing[J]. Mol Cell,2008,29:92-101.
[55].Lee HJ,Kim MS, Shin JM, et al. The expression patterns of deubiquitinating enzymes,USP22and Usp22[J]. Gene ExpressionPatterns 6,2006,277-284.
[56].Satija YK, Bhardwaj A, Das S. A portrayal of E3 ubiquitin ligases and deubiquitylases in cancer[J]. Int J Cancer,2013,133(12):2759-68.
[57].Samara NL, Wolberger C. A new chapter in the transcription SAGA[J]. Curr Opin Struct Biol,2011;21(6):767-74.
[58].Liu X, Teisfai J, Martinez E, et al. C-MYC transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for transcription activation[J] J Biol Chem,2003; 278(22):20405-20412.
[59].Liu YL, Jiang SX, Yang YM, et al. USP22 acts as an oncogene by the activation of BMI-1-mediated INK4a/ARF pathway and Akt pathway[J]. Cell Biochem Biophys, 2012,62(1):229-35.
[60].Xu H, Liu YL, Yang Ym, et al. Knock-down of ubiquitin-specific protease 22 by micro-RNA interference inhibits colorectal cancer growth[J]. International Journal of Colorectal Disease,2012,27:21-30.
[61].Atanassov BS, Dent SYR. USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1[J]. Embo Reports,2011,12:924-930.
[62].Lv L, Xiao XY, Gu ZH et al. Silencing USP22 by asymmetric structure of interfering RNA inhibits proliferation and induces cell cycle arrest in bladder cancer cells[J]. Mol Cell Biochem,2011,346(1-2):11-21.
[63].Sridharan R1, Tchieu J, Mason MJ, et al. Role of the murine reprogramming factors in the induction of pluripotency[J]. Cell,2009,136(2):364-77.
[64].Sussman RT, Stanek TJ, Esteso P, et al. The epigenetic modifier ubiquitin-specific protease 22 (USP22) regulates embryonic stem cell differentiation via transcriptional repression of sex-determining region Y-box 2 (SOX2)[J]. J Biol Chem,2013,288(33):24234-46.
[65].Dai W, Yao Y, Zhou Q, et al. Ubiquitin-specific peptidase 22, a histone deubiquitinating enzyme, is a novel poor prognostic factor for salivary adenoid cystic carcinoma[J]. PLoS One,2014,9(1):e87148.
[66].Yang M, Liu YD, Wang YY, et al. Ubiquitin-specific protease 22:a novel molecular biomarker in cervical cancer prognosis and therapeutics [J]. Tumour Biol, 2014,35(2):929-3.
[67].Piao S, Ma J, Wang W, et al. Increased expression of USP22 is associated with disease progression and patient prognosis of salivary duct carcinoma[J]. Oral Oncol, 2013,49(8):796-801.
[68].Wang H, Li YP, Chen JH, et al. Prognostic significance of USP22 as an oncogene in papillary thyroid carcinoma[J]. Tumour Biol,2013,34(3):1635-9.
[69].Ning J, Zhang J, Liu W, et al.Overexpression of ubiquitin-specific protease 22 predicts poor survival in patients with early-stage non-small cell lung cancer [J]. Eur J Histochem,2012,56(4):e46.
[70].Piao S, Liu Y, Hu J, et al. USP22 is useful as a novel molecular marker for predicting disease progression and patient prognosis of oral squamous cell carcinoma[J]. PLoS One,2012,7(8):e42540.
[71].Li J, Wang Z, Li Y, et al. USP22 nuclear expression is significantly associated with progression and unfavorable clinical outcome in human esophageal squamous cell carcinoma[J]. J Cancer Res Clin Oncol,2012,138(8):1291-7.
[72].Liu YL, Yang YM, Xu H, et al. Aberrant expression of USP22 is associated with liver metastasis and poor prognosis of colorectal cancer [J]. J Sur Oncol,2011, 103(3):283-289.
[73].Zhang Y, Yao L, Zhang X, et al. Elevated expression of USP22 in correlation with poor prognosis in patients with invasive breast cancer [J]. J Cancer Res Clin Onco,2011,137(8):1245-53.
[74].Yang DD, Cui BB, Sun LY, et al. The co-expression of USP22 and BMI-1 may promote cancer progression and predict therapy failure in gastric carcinoma.Cell Biochem Biophys,2011,61(3):703-10.
[75].Luo Y, Zeng FQ, Gu ZH, et al. Quantitative analysis of the putative cancer stem cell marker USP22 mRNA in the transitional cell carcinoma of the bladder and the relationship between USP22 and the grading of tumor[J]. J Clin Urol,2009, 24(2):140-144.
[76].Liu Y, Yang Y, Xu H, et al. Implication of USP22 in the regulation of BMI-1, c-Myc, p16INK4a, p14ARF, and cyclin D2 expression in primary colorectal carcinomas[J]. Diagn Mol Patho,2010,19(4):194-200.
[77].Schrecengost RS, Dean JL, Goodwin JF, et al. USP22 regulates oncogenic signaling pathways to drive lethal cancer progression[J]. Cancer Res,2014, 74(1):272-86.
[78].Daniel J A, Grant PA. Multi-tasking on chromatin with the SAGA coactivator complexes [J]. Mutat Res,2007,618(122):135-148.
[79].Liu YL, Yang YM, Xu H, et al.Increased expression of ubiquitin-specific protease 22 can promote cancer progression and predict therapy failure in human colorectal cancer[J]. J Gastroenterol Hepatol,2010,25(11):1800-5
[80].Xiong JJ, Gan LJ, Lin L, et al. Construction and identification of eukaryotic expression plasmid expressing siRNA targeting USP22 gene[J]. Sichuan Da Xue Xue Bao Yi Xue Ban,2011,42(2):166-9.
[81].Ling SB, Sun DG, Tang B, et al. Knock-down of USP22 by small interfering RNA interference inhibits HepG2 cell proliferation and induces cell cycle arrest[J]. Cell Mol Biol (Noisy-le-grand),2012,58:1803-8.
[82].Hu J, Liu YL, Piao SL, et al. Expression patterns of USP22 and potential targets BMI-1, PTEN, p-AKT in non-small-cell lung cancer [J]. Lung Cancer,2012, 77(3):593-9.
[83].Liu S, Dontu G, Mantle ID, et al. Hedgehog signaling and BMI-1 regulate self-re newal of normal and malignant human mammary stem cells[J]. Cancer Res, 2006,66(12):6063-6071.
[84].A1-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells[J].Oncogene, 2004,23(43):7274-7282.
[85].Davie JR, Murphy LC. Level of ubiquitinated histone H2B in chromatin is coupled to ongoing transcription[J]. Biochemistry,1990,29(20):4752-7
[86].Schwartz AL, Trausch JS, Ciechanover A, et al.Immunoelectron microscopic localization of the ubiquitin-activating enzyme El in HepG2 cells[J]. Proc Natl Acad Sci USA,1992,89(12):5542-6.
[87].Ciechanover A, Orian A, Schwartz AL, et al.The ubiquitin-mediated proteolytic pathway:mode of action and clinical implications[J]. J Cell Biochem Suppl,2000, 34:40-51.
[88].Wilkinson KD. Ubiquitin-dependent signaling:the role of ubiquitination in the response of cells to their environment[J]. J Nutr,1999,129(11):1933-6.
[89].Mimnaugh EG, Bonvini P, Neckers L, et al. The measurement of ubiquitin and ubiquitinated proteins[J]. Electrophoresis,1999,20(2):418-28.
[90].Weissman AM. Regulating protein degradation by ubiquitination[J].Immunol Today,1997,18(4):189-98.
[91].Luscher B, Vervoorts J. Regulation of gene transcription by the oncoprotein MYC[J].Gene,2012,;494(2):145-60.
[92].Muller J, Eilers M. Ubiquitination of Myc:proteasomal degradation and beyond[J]. Ernst Schering Found Symp Proc,2008(1):99-113.
[93].Sun Y, Li H. Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase[J]. Protein Cell,2013,4(2):103-16.
[94].Jariel-Encontre I, Bossis G, Piechaczyk M.Ubiquitin-independent degradation of proteins by the proteasome[J]. Biochim Biophys Acta,2008,1786(2):153-77.
[95].Ichihara A, Tanaka K. Roles of proteasomes in cell growth[J]. Mol Biol Rep, 1995,21(1):49-52.
[96].Ingley E.Src family kinases:regulation of their activities, levels and identification of new pathways[J]. Biochim Biophys Acta,2008,1784(1):56-65.
[97].Ben-Neriah Y.Regulatory functions of ubiquitination in the immune system[J]. Nat Immunol,2002,3(1):20-6.
[98].Moutoussamy S, Kelly PA, Finidori J, et al. Growth-hormone-receptor and cytokine-receptor-family signaling[J]. Eur J Biochem,1998,255(1):1-11.
[99].Nguyen LK, Kolch W, Kholodenko BN. When ubiquitination meets phosphorylation:a systems biology perspective of EGFR/MAPK signalling [J]. Cell Commun Signal,2013,11:52.
[100].Xiu X, Lu ZM.Ubiquitination-mediated degradation of epidermal growth factor receptor[J]. Zhong guo Yi Xue Ke Xue Yuan Xue Bao,2005,27(1):120-7.
[101].Stamos JL, Weis WI. The (3-catenin destruction complex[J]. Cold Spring Harb PerspectBiol,2013,5(1):a007898.
[102].Kikuchi A, Kishida S. Abnormal regulation of beta-catenin degradation through ubiquitination as a mechanism of carcinogenesis[J]. Tanpakushitsu Kakusan Koso, 2006,51(10 Suppl):1271-6.
[103].Kikuchi A, Kishida S, Yamamoto H. Regulation of Wnt signaling by protein-protein interaction and post-translational modifications[J]. Exp Mol Med, 2006,38(1):1-10.
[104].Fuchs SY.The role of ubiquitin-proteasome pathway in oncogenic signaling[J]. Cancer Biol Ther,2002,1(4):337-41.
[105].Mohapatra B, Ahmad G, Nadeau S, et al. Protein tyrosine kinase regulation by ubiquitination:critical roles of Cbl-family ubiquitin ligases[J]. Biochim Biophys Acta, 2013,1833(1):122-39.
[106].Severe N, Marie P. Implication of the ubiquitin ligase c-Cbl in bone formation and tumorigenesis[J].Med Sci (Paris),2012,28(11):970-5.
[107].Gay DL, Ramon H, Oliver PM. Cbl-and Nedd4-family ubiquitin ligases: balancing tolerance and immunity[J]. Immunol Res,2008,42(1-3):51-64.
[108].Ingley E.Src family kinases:regulation of their activities, levels and identification of new pathways[J]. Biochim Biophys Acta.2008,1784(1):56-65.
[109].Venuprasad K.Cbl-b and itch:key regulators of peripheral T-cell tolerance [J]. Cancer Res,2010,70(8):3009-12.
[110].Ardley HC, Robinson PA.E3 ubiquitin ligases[J]. Essays Biochem,2005, 41:15-30.
[111].Lu Z, Hunter T. Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors [J]. Cell Cycle,2010,9(12):2342-52.
[112].Kotoshiba S, Nakayama K.The degradation of p27 and cancer[J]. Nihon Rinsho. 2005,63(11):2047-56.
[113].Stewart D, Ghosh A, Matlashewski G. Involvement of nuclear export in human papillomavirus type 18 E6-mediated ubiquitination and degradation of p53[J]. J Virol, 2005,79(14):8773-83.
[114].Gewin L, Myers H, Kiyono T, et al. Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex[J]. Genes Dev,2004,18(18):2269-82.
[115].Ma J, Martin JD, Xue Y, et al. C-terminal region of USP7/HAUSP is critical for deubiquitination activity and contains a second mdm2/p53 binding site[J]. Arch Biochem Biophys,2010,503(2):207-12.
[116].Song MS, Song SJ, Kim SY, et al. The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex[J]. EMBO J,2008,27(13):1863-74.
[117].Becker K, Marchenko ND, Palacios G. A role of HAUSP in tumor suppression in a human colon carcinoma xenograft model[J]. Cell Cycle,2008,7(9):1205-13.
[118].Brazhnik P, Kohn KW. HAUSP-regulated switch from auto-to p53 ubiquitination by Mdm2 (in silico discovery)[J]. Math Biosci,2007,210(1):60-77.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |