TRIM32调控病毒诱导的Ⅰ型干扰素表达的分子机制
摘要
细胞抗病毒天然免疫是机体抵御病毒入侵的第一道防线,具有反应快速、普遍性、多样性等特点。病毒感染细胞后,存在于机体内的模式识别受体(pattern recognition receptor, PRR)能够识别病毒的病原相关分子模式(pathogen-associated molecular pattern, PAMP),从而激活PRR介导的Ⅰ型干扰素表达。Ⅰ型干扰素分泌到细胞外与细胞表面的干扰素受体(IFN receptor, IFNR)结合,并通过JAK-STAT信号通路诱导大量抗病毒基因表达,这些蛋白分子具有抑制病毒复制和诱导被感染细胞凋亡等功能,从而抵抗病毒入侵。Ⅰ型干扰素表达需要依赖多种转录因子协同合作从而激活其转录活性,其中转录因子NF-κB (nulear factor-kappa B)和IRF3(interferon regulatory factor3)发挥至关重要的作用。
MITA是定位于线粒体和内质网上的相关膜蛋白分子。MITA(?)(?)RNA病毒和DNA病毒诱导的Ⅰ型干扰素表达及细胞抗病毒反应至关重要。泛素化修饰是病毒诱导Ⅰ型干扰素产生过程中的重要调节机制,病毒感染细胞能引起MITA泛素化。我们先前的研究结果发现RNF5能够催化MITA泛素化降解从而抑制病毒诱导的Ⅰ型干扰素的表达。接下来,我们进一步在E3泛素连接酶的表达文库中通过泛素化检测实验筛选能够泛素化MITA的E3泛素连接酶,确认是否还存在其它的E3泛素连接酶参与病毒诱导的MITA的泛素化过程。在本项研究工作中,我们鉴定出一个TRIM (tripartite motif protein)蛋白家族的分子TRIM32,它既能特异性地泛素化MITA又可以明显地增强MITA介导的Ⅰ型干扰素表达。过量表达TRIM32可以激活Ⅰ型干扰素和NF-κB下游基因的表达,同时,也促进了RNA病毒和DNA病毒诱导的Ⅰ型干扰素的产生。而下调TRIM32的表达则有相反的影响。野生型TRIM32而非TRIM32缺失RING结构域的突变体和E3泛素连接酶活性丧失的点突变载体能够泛素化MITA,同时我们还发现TRIM32突变体可以作为显性抑制子阻断细胞抗病毒反应。空斑实验证明,过量表达TRIM32可以抑制病毒复制,而过量表达其突变体或用TRIM32-RNAi下调TRIM32的表达能够促进病毒复制。这些实验结果无不一致地表明,TRIM32依赖其RING结构域的E3泛素连接酶活性正向调节细胞抗病毒免疫应答。在机理方面,免疫共沉淀实验表明TRIM32与MITA相互作用,并且共定位于线粒体和内质网上。体外和体内泛素化实验显示,MITA是TRIM32的直接底物,并且TRIM32催化MITA发生Lys-63位连接的泛素化。通过构建MITA的一系列赖氨酸残基点突变载体,我们发现TRIM32靶向MITA蛋白分子的第20、150、224和236位赖氨酸位点发生泛素化,而这四个位点正是MITA自身功能发挥所必需的。此外,TRIM32还能介导MITA(?)下游信号分子TBK1的相互作用。总而言之,具有E3泛索连接酶活性的TRIM32能够通过催化MITA发生Lys-63位连接的泛素化从而激活下游信号转导,正调控细胞抗病毒天然免疫应答。
目前,研究者们发现E3泛索连接酶TRIM32能够靶向多种蛋白分子发生泛素化降解从而参与癌症、肌肉萎缩症和神经系统疾病等的病变过程。在本项研究中,我们首次发现了TRIM32在细胞抗病毒反应中的重要作用以及催化靶蛋白发生Lys-63位连接的泛素化激活功能。然而,本项研究工作还存在不足之处,这些实验仅局限于细胞水平的研究,因此,未来我们将通过构建TRIM32敲除小鼠进步探知它在动物水平上的抗病毒效应。
Cellular antiviral innate immunity is the first line of host defense against invading viruses. Upon viral infection, innate immune response is initiated by the recognition of viral pathogen-associated molecular patterns (PAMPs) by germline-encoded pattern recognition receptors (PRRs) to activate the expression of type I interferons. The secreted type I interferons are recognized by interferon receptors (IFNRs) and further induce expression of a wide variety of antiviral genes through the JAK-STAT signaling pathway. The transcriptional activation of type I interferons requires several transcription factors, including nuclear factor-kappa B (NF-κB) and interferon regulatory factor (IRF3).
MITA has been identified as a mitochondrion-and ER-associated membrane protein that is critically involved in type I interferon induction and antiviral innate immunity in response to both RNA and DNA viral infection. Virus-triggered type I interferon induction and antiviral response are heavily regulated by ubiquitination of the key components involved in these pathways. Viral infection can lead to ubiquitination of MITA, our previous study has demonstrated that an E3ubiquitin ligase RNF5catalyzes K48-linked ubiquitination of MITA and inhibits virus-triggered type I interferon induction. Next, we further screened our E3ubiquitin ligase expression library to determine whether other E3ligases are involved in virus-induced ubiquitination of MITA. In this study, we identified a TRIM (tripartite motif protein) family member, TRIM32, that specifically ubiquitinated MITA and dramatically enhanced MITA-mediated induction of IFN-β. Overexpression of TRIM32led to activation of NF-κB and IFN-β promoter and potentiated virus-triggered expression of IFNB1and NF-κB downstream genes. while, knockdown of TRIM32had opposite effects. In addition, we found that wild-type TRIM32but not TRIM32-△R or TRIM32(C39S), two enzymatic inactive mutants, ubiquitinated MITA and these mutants could act as dominant negative regulators to abrogate cellular antiviral response. VSV plaque assays indicated that overexpression of TRIM32inhibited virus replication, while overexpression of the enzymatic inactive mutants or knockdown TRIM32by TRIM32-RNAi potentiated virus replication. These findings suggest that TRIM32positively regulates cellular antiviral immune which depends on its E3ubiquitin ligase activity. Mechanically, TRIM32interacted with MITA, and was located at the mitochondria and endoplasmic reticulum. TRIM32directly targeted MITA for K63-linked ubiquitination at K20/150/224/236of MITA, which promoted the interaction of MITA with TBK1. Collectively, TRIM32is a key regulatory protein for innate immunity against both RNA and DNA viruses by targeting MITA for K63-linked ubiquitination.
TRIM32has been shown to induce ubiquitination and degradation of multiple substrates and participate in diverse pathological processes including carcinogenesis, muscular dystrophy and nervous system diseases. Our study for the first time demonstrates that TRIM32plays a key regulatory role in cellular antiviral immunity and can target a protein for K63-linked ubiquitination, thereby promoting its activation. Future studies are required to examine whether TRIM32is required for host defense against DNA or RNA viral infection at animal level by generating TRIM32-deficient mice.
MITA是定位于线粒体和内质网上的相关膜蛋白分子。MITA(?)(?)RNA病毒和DNA病毒诱导的Ⅰ型干扰素表达及细胞抗病毒反应至关重要。泛素化修饰是病毒诱导Ⅰ型干扰素产生过程中的重要调节机制,病毒感染细胞能引起MITA泛素化。我们先前的研究结果发现RNF5能够催化MITA泛素化降解从而抑制病毒诱导的Ⅰ型干扰素的表达。接下来,我们进一步在E3泛素连接酶的表达文库中通过泛素化检测实验筛选能够泛素化MITA的E3泛素连接酶,确认是否还存在其它的E3泛素连接酶参与病毒诱导的MITA的泛素化过程。在本项研究工作中,我们鉴定出一个TRIM (tripartite motif protein)蛋白家族的分子TRIM32,它既能特异性地泛素化MITA又可以明显地增强MITA介导的Ⅰ型干扰素表达。过量表达TRIM32可以激活Ⅰ型干扰素和NF-κB下游基因的表达,同时,也促进了RNA病毒和DNA病毒诱导的Ⅰ型干扰素的产生。而下调TRIM32的表达则有相反的影响。野生型TRIM32而非TRIM32缺失RING结构域的突变体和E3泛素连接酶活性丧失的点突变载体能够泛素化MITA,同时我们还发现TRIM32突变体可以作为显性抑制子阻断细胞抗病毒反应。空斑实验证明,过量表达TRIM32可以抑制病毒复制,而过量表达其突变体或用TRIM32-RNAi下调TRIM32的表达能够促进病毒复制。这些实验结果无不一致地表明,TRIM32依赖其RING结构域的E3泛素连接酶活性正向调节细胞抗病毒免疫应答。在机理方面,免疫共沉淀实验表明TRIM32与MITA相互作用,并且共定位于线粒体和内质网上。体外和体内泛素化实验显示,MITA是TRIM32的直接底物,并且TRIM32催化MITA发生Lys-63位连接的泛素化。通过构建MITA的一系列赖氨酸残基点突变载体,我们发现TRIM32靶向MITA蛋白分子的第20、150、224和236位赖氨酸位点发生泛素化,而这四个位点正是MITA自身功能发挥所必需的。此外,TRIM32还能介导MITA(?)下游信号分子TBK1的相互作用。总而言之,具有E3泛索连接酶活性的TRIM32能够通过催化MITA发生Lys-63位连接的泛素化从而激活下游信号转导,正调控细胞抗病毒天然免疫应答。
目前,研究者们发现E3泛索连接酶TRIM32能够靶向多种蛋白分子发生泛素化降解从而参与癌症、肌肉萎缩症和神经系统疾病等的病变过程。在本项研究中,我们首次发现了TRIM32在细胞抗病毒反应中的重要作用以及催化靶蛋白发生Lys-63位连接的泛素化激活功能。然而,本项研究工作还存在不足之处,这些实验仅局限于细胞水平的研究,因此,未来我们将通过构建TRIM32敲除小鼠进步探知它在动物水平上的抗病毒效应。
Cellular antiviral innate immunity is the first line of host defense against invading viruses. Upon viral infection, innate immune response is initiated by the recognition of viral pathogen-associated molecular patterns (PAMPs) by germline-encoded pattern recognition receptors (PRRs) to activate the expression of type I interferons. The secreted type I interferons are recognized by interferon receptors (IFNRs) and further induce expression of a wide variety of antiviral genes through the JAK-STAT signaling pathway. The transcriptional activation of type I interferons requires several transcription factors, including nuclear factor-kappa B (NF-κB) and interferon regulatory factor (IRF3).
MITA has been identified as a mitochondrion-and ER-associated membrane protein that is critically involved in type I interferon induction and antiviral innate immunity in response to both RNA and DNA viral infection. Virus-triggered type I interferon induction and antiviral response are heavily regulated by ubiquitination of the key components involved in these pathways. Viral infection can lead to ubiquitination of MITA, our previous study has demonstrated that an E3ubiquitin ligase RNF5catalyzes K48-linked ubiquitination of MITA and inhibits virus-triggered type I interferon induction. Next, we further screened our E3ubiquitin ligase expression library to determine whether other E3ligases are involved in virus-induced ubiquitination of MITA. In this study, we identified a TRIM (tripartite motif protein) family member, TRIM32, that specifically ubiquitinated MITA and dramatically enhanced MITA-mediated induction of IFN-β. Overexpression of TRIM32led to activation of NF-κB and IFN-β promoter and potentiated virus-triggered expression of IFNB1and NF-κB downstream genes. while, knockdown of TRIM32had opposite effects. In addition, we found that wild-type TRIM32but not TRIM32-△R or TRIM32(C39S), two enzymatic inactive mutants, ubiquitinated MITA and these mutants could act as dominant negative regulators to abrogate cellular antiviral response. VSV plaque assays indicated that overexpression of TRIM32inhibited virus replication, while overexpression of the enzymatic inactive mutants or knockdown TRIM32by TRIM32-RNAi potentiated virus replication. These findings suggest that TRIM32positively regulates cellular antiviral immune which depends on its E3ubiquitin ligase activity. Mechanically, TRIM32interacted with MITA, and was located at the mitochondria and endoplasmic reticulum. TRIM32directly targeted MITA for K63-linked ubiquitination at K20/150/224/236of MITA, which promoted the interaction of MITA with TBK1. Collectively, TRIM32is a key regulatory protein for innate immunity against both RNA and DNA viruses by targeting MITA for K63-linked ubiquitination.
TRIM32has been shown to induce ubiquitination and degradation of multiple substrates and participate in diverse pathological processes including carcinogenesis, muscular dystrophy and nervous system diseases. Our study for the first time demonstrates that TRIM32plays a key regulatory role in cellular antiviral immunity and can target a protein for K63-linked ubiquitination, thereby promoting its activation. Future studies are required to examine whether TRIM32is required for host defense against DNA or RNA viral infection at animal level by generating TRIM32-deficient mice.
引文
[1]GANZ T. Defensins:antimicrobial peptides of innate immunity [J]. Nature reviews Immunology, 2003,3(9):710-20.
[2]KLOTMAN M E, CHANG T L. Defensins in innate antiviral immunity [J]. Nature reviews Immunology,2006,6(6):447-56.
[3]NATHAN C. Neutrophils and immunity:challenges and opportunities [J]. Nature reviews Immunology,2006,6(3):173-82.
[4]BIRON C A, NGUYEN K B, PIEN G C, COUSENS L P, SALAZAR-MATHER T P. Natural killer cells in antiviral defense:function and regulation by innate cytokines [J]. Annual review of immunology,1999,17(189-220.
[5]CARROLL M C. The role of complement and complement receptors in induction and regulation of immunity [J]. Annual review of immunology,1998,16(545-68.
[6]LARSEN G L, HENSON P M. Mediators of inflammation [J]. Annual review of immunology, 1983,1(335-59.
[7]BEUTLER B, CERAMI A. The biology of cachectin/TNF-a primary mediator of the host response [J]. Annual review of immunology,1989,7(625-55.
[8]ISAACS A, LINDENMANN J. Virus interference. I. The interferon [J]. Proc R Soc Lond B Biol Sci,1957,147(927):258-67. [9] SADLER A J, WILLIAMS B R. Interferon-inducible antiviral effectors [J]. Nature reviews
Immunology,2008,8(7):559-68.
[10]JANEWAY C A, JR., MEDZHITOV R. Innate immune recognition [J]. Annual review of immunology,2002,20(197-216.
[11]WRIGHT J R. Immunoregulatory functions of surfactant proteins [J]. Nature reviews Immunology,2005,5(1):58-68.
[12]AKIRA S, TAKEDA K. Toll-like receptor signalling [J]. Nature reviews Immunology,2004,4(7): 499-511.
[13]BEUTLER B. Toll-like receptors and their place in immunology. Where does the immune response to infection begin? [J]. Nature reviews Immunology,2004,4(7):498.
[14]MEDZHITOV R. Toll-like receptors and innate immunity [J]. Nature reviews Immunology,2001, 1(2):135-45.
[15]AKIRA S, UEMATSU S, TAKEUCHI O. Pathogen recognition and innate immunity [J]. Cell, 2006,124(4):783-801.
[16]YONEYAMA M, FUJITA T. RNA recognition and signal transduction by RIG-I-like receptors [J]. Immunological reviews,2009,227(1):54-65.
[17]YONEYAMA M, KIKUCHI M, NATSUKAWA T, SHINOBU N, IMAIZUMI T, MIYAGISHI M, TAIRA K, AKIRA S, FUJITA T. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses [J]. Nature immunology,2004,5(7):730-7.
[18]CUI S, EISENACHER K, KIRCHHOFER A, BRZOZKA K, LAMMENS A, LAMMENS K, FUJITA T, CONZELMANN K K, KRUG A, HOPFNER K P. The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I [J]. Molecular cell,2008,29(2):169-79.
[19]TAKAHASI K, YONEYAMA M, NISHIHORI T, HIRAI R, KUMETA H, NARITA R, GALE M. JR., INAGAKI F, FUJITA T. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses [J]. Molecular cell,2008,29(4):428-40.
[20]YONEYAMA M, FUJITA T. Structural mechanism of RNA recognition by the RIG-I-like receptors [J]. Immunity,2008,29(2):178-81.
[21]KANG D C, GOPALKRISHNAN R V, WU Q, JANKOWSKY E, PYLE A M, FISHER P B. mda-5:An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties [J]. Proceedings of the National Academy of Sciences of the United States of America,2002,99(2):637-42.
[22]WU B, PEISLEY A, RICHARDS C, YAO H, ZENG X, LIN C, CHU F, WALZ T, HUR S. Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5 [J]. Cell,2013,152(1-2):276-89.
[23]ROTHENFUSSER S, GOUTAGNY N, DIPERNA G, GONG M, MONKS B G, SCHOENEMEYER A, YAMAMOTO M, AKIRA S, FITZGERALD K A. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I [J]. J Immunol, 2005,175(8):5260-8.
[24]LOO Y M, GALE M, JR. Immune signaling by RIG-I-like receptors [J]. Immunity,2011,34(5): 680-92.
[25]KATO H, TAKEUCHI O, MIKAMO-SATOH E, HIRAI R, KAWAI T, MATSUSHITA K, HIIRAGI A, DERMODY T S, FUJITA T, AKIRA S. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5 [J]. The Journal of experimental medicine,2008,205(7):1601-10.
[26]HORNUNG V, ELLEGAST J, KIM S, BRZOZKA K, JUNG A, KATO H, POECK H, AKIRA S, CONZELMANN K K, SCHLEE M, ENDRES S, HARTMANN G.5'-Triphosphate RNA is the ligand for RIG-I [J]. Science,2006,314(5801):994-7.
[27]PICHLMAIR A, SCHULZ O, TAN C P, NASLUND T I, LILJESTROM P, WEBER F, REIS E SOUSA C. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates [J]. Science,2006,314(5801):997-1001.
[28]SCHLEE M, ROTH A, HORNUNG V, HAGMANN C A, WIMMENAUER V, BARCHET W, COCH C, JANKE M, MIHAILOVIC A, WARDLE G, JURANEK S, KATO H, KAWAI T, POECK H, FITZGERALD K A, TAKEUCHI O, AKIRA S, TUSCHL T, LATZ E, LUDWIG J, HARTMANN G. Recognition of 5'triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus [J]. Immunity,2009,31(1):25-34.
[29]PEISLEY A, LIN C, WU B, ORME-JOHNSON M, LIU M, WALZ T, HUR S. Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition [J]. Proceedings of the National Academy of Sciences of the United States of America,2011,108(52):21010-5.
[30]PEISLEY A, JO M H, LIN C, WU B, ORME-JOHNSON M, WALZ T, HOHNG S, HUR S. Kinetic mechanism for viral dsRNA length discrimination by MDA5 filaments [J]. Proceedings of the National Academy of Sciences of the United States of America,2012,109(49):E3340-9.
[31]YONEYAMA M, KIKUCHI M, MATSUMOTO K, IMAIZUMI T, MIYAGISHI M, TAIRA K, FOY E, LOO Y M, GALE M, JR., AKIRA S, YONEHARA S, KATO A, FUJITA T. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity [J]. J Immunol,2005,175(5):2851-8.
[32]VENKATARAMAN T, VALDES M, ELSBY R, KAKUTA S, CACERES G, SAIJO S, IWAKURA Y, BARBER G N. Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses [J]. J Immunol,2007,178(10):6444-55.
[33]TAKAHASI K, KUMETA H, TSUDUKI N, NARITA R, SHIGEMOTO T, HIRAI R, YONEYAMA M, HORIUCHI M, OGURA K, FUJITA T, INAGAKI F. Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains:identification of the RNA recognition loop in RIG-I-like receptors [J]. The Journal of biological chemistry,2009,284(26):17465-74.
[34]PIPPIG D A, HELLMUTH J C, CUI S, KIRCHHOFER A, LAMMENS K, LAMMENS A, SCHMIDT A, ROTHENFUSSER S, HOPFNER K P. The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA [J]. Nucleic acids research,2009,37(6):2014-25.
[35]SATOH T, KATO H, KUMAGAI Y, YONEYAMA M, SATO S, MATSUSHITA K, TSUJIMURA T, FUJITA T, AKIRA S, TAKEUCHI O. LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses [J]. Proceedings of the National Academy of Sciences of the United States of America,2010,107(4):1512-7.
[36]TAKEUCHI O, AKIRA S. Innate immunity to virus infection [J]. Immunological reviews,2009, 227(1):75-86.
[37]YE Z, TING J P. NLR, the nucleotide-binding domain leucine-rich repeat containing gene family [J]. Current opinion in immunology,2008,20(1):3-9.
[38]FRANCHI L, WARNER N, VIANI K, NUNEZ G. Function of Nod-like receptors in microbial recognition and host defense [J]. Immunological reviews,2009,227(1):106-28.
[39]SHAW M H, REIMER T, KIM Y G, NUNEZ G. NOD-like receptors (NLRs):bona fide intracellular microbial sensors [J]. Current opinion in immunology,2008,20(4):377-82.
[40]SABBAH A, CHANG T H, HARNACK R, FROHLICH V, TOMINAGAK, DUBE P H, XIANG Y, BOSE S. Activation of innate immune antiviral responses by Nod2 [J]. Nature immunology,2009, 10(10):1073-80.
[41]ISHII K J, COBAN C, KATO H, TAKAHASHI K, TORII Y, TAKESHITA F, LUDWIG H, SUTTER G, SUZUKI K, HEMMI H, SATO S, YAMAMOTO M, UEMATSU S, KAWAI T, TAKEUCHI O, AKIRA S. A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA [J]. Nature immunology,2006,7(1):40-8.
[42]ISHII K J, KAWAGOE T, KOYAMA S, MATSUI K, KUMAR H, KAWAI T, UEMATSU S, TAKEUCHI O, TAKESHITA F, COBAN C, AKIRA S. TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines [J]. Nature,2008,451(7179):725-9.
[43]TAKAOKA A, WANG Z, CHOI M K, YANAI H, NEGISHI H, BAN T, LU Y, MIYAGISHI M, KODAMA T, HONDA K, OHBA Y, TANIGUCHI T. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response [J]. Nature,2007,448(7152):501-5.
[44]LIPPMANN J, ROTHENBURG S, DEIGENDESCH N, EITEL J, MEIXENBERGER K, VAN LAAK V, SLEVOGT H, N'GUESSAN P D, HIPPENSTIEL S, CHAKRABORTY T, FLIEGER A, SUTTORP N, OPITZ B. IFNbeta responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI) [J]. Cellular microbiology,2008,10(12): 2579-88.
[45]KAISER W J, UPTON J W, MOCARSKI E S. Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors [J]. J Immunol,2008,181(9):6427-34.
[46]BURCKSTUMMER T, BAUMANN C, BLUML S, DIXIT E, DURNBERGER G, JAHN H, PLANYAVSKY M, BILBAN M, COLINGE J, BENNETT K L, SUPERTI-FURGA G. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome [J]. Nature immunology,2009,10(3):266-72.
[47]FERNANDES-ALNEMRI T, YU J W, DATTA P, WU J, ALNEMRI E S. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA [J]. Nature,2009,458(7237):509-13.
[48]HORNUNG V, ABLASSER A, CHARREL-DENNIS M, BAUERNFEIND F, HORVATH G, CAFFREY D R, LATZ E, FITZGERALD K A. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC [J]. Nature,2009,458(7237):514-8.
[49]ZHONG B, YANG Y, LI S, WANG Y Y, LI Y, DIAO F, LEI C, HE X, ZHANG L, TIEN P, SHU H B. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation [J]. Immunity,2008,29(4):538-50.
[50]ISHIKAWA H, MA Z, BARBER G N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity [J]. Nature,2009,461(7265):788-92.
[51]CHIU Y H, MACMILLAN J B, CHEN Z J. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway [J]. Cell,2009,138(3):576-91.
[52]UNTERHOLZNER L, KEATING S E, BARAN M, HORAN K A, JENSEN S B, SHARMA S, SIROIS C M, JIN T, LATZ E, XIAO T S, FITZGERALD K A, PALUDAN S R, BOWIE A G. IFI16 is an innate immune sensor for intracellular DNA [J]. Nature immunology,2010,11(11):997-1004.
[53]YANG P, AN H, LIU X, WEN M, ZHENG Y, RUI Y, CAO X. The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a beta-catenin-dependent pathway [J]. Nature immunology,2010,11(6):487-94.
[54]KIM T, PAZHOOR S, BAO M, ZHANG Z, HANABUCHI S, FACCHINETTI V, BOVER L, PLUMAS J, CHAPEROT L, QIN J, LIU Y J. Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells [J]. Proceedings of the National Academy of Sciences of the United States of America,2010,107(34): 15181-6.
[55]ZHANG Z, YUAN B, BAO M, LU N, KIM T, LIU Y J. The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells [J]. Nature immunology,2011,12(10):959-65.
[56]PARVATIYAR K, ZHANG Z, TELES R M, OUYANG S, JIANG Y, IYER S S, ZAVER S A, SCHENK M, ZENG S, ZHONG W, LIU Z J, MODLIN R L, LIU Y J, CHENG G. The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response [J]. Nature immunology,2012,13(12):1155-61.
[57]WU J, SUN L, CHEN X, DU F, SHI H, CHEN C, CHEN Z J. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA [J]. Science,2013, 339(6121):826-30.
[58]SUN L, WU J, DU F, CHEN X, CHEN Z J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway [J]. Science,2013,339(6121):786-91.
[59]NIE Y, WANG Y Y. Innate immune responses to DNA viruses [J]. Protein & cell,2013,4(1):1-7.
[60]KAWAI T, AKIRA S. The roles of TLRs, RLRs and NLRs in pathogen recognition [J]. International immunology,2009,21(4):317-37.
[61]THEOFILOPOULOS A N, BACCALA R, BEUTLER B, KONO D H. Type I interferons (alpha/beta) in immunity and autoimmunity [J]. Annual review of immunology,2005,23(307-36.
[62]GRANDVAUX N, SERVANT M J, TENOEVER B, SEN G C, BALACHANDRAN S, BARBER G N, LIN R, HISCOTT J. Transcriptional profiling of interferon regulatory factor 3 target genes:direct involvement in the regulation of interferon-stimulated genes [J]. Journal of virology,2002,76(11): 5532-9.
[63]SAMUEL C E. Antiviral actions of interferons [J]. Clinical microbiology reviews,2001,14(4): 778-809, table of contents.
[64]TANIGUCHI T, MANTEI N, SCHWARZSTEIN M, NAGATA S, MURAMATSU M, WEISSMANN C. Human leukocyte and fibroblast interferons are structurally related [J]. Nature,1980, 285(5766):547-9.
[65]THANOS D, MANIATIS T. Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome [J]. Cell,1995,83(7):1091-100.
[66]WATHELET M G, LIN C H, PAREKH B S, RONCO L V, HOWLEY P M, MANIATIS T. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo [J]. Molecular cell,1998,1(4):507-18.
[67]AGALIOTI T, LOMVARDAS S, PAREKH B, YIE J, MANIATIS T, THANOS D. Ordered recruitment of chromatin modifying and general transcription factors to the IFN-beta promoter [J]. Cell, 2000,103(4):667-78.
[68]HONDA K, TAKAOKA A, TANIGUCHI T. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors [J]. Immunity,2006,25(3):349-60.
[69]RAJ N B, ISRAELI R, KELLUM M, PITHA P M. Upstream regulatory elements of murine alpha 4-interferon gene confer inducibility and cell type-restricted expression [J]. The Journal of biological chemistry,1989,264(19):11149-57.
[70]RYALS J, DIERKS P, RAGG H, WEISSMANN C. A 46-nucleotide promoter segment from an IFN-alpha gene renders an unrelated promoter inducible by virus [J]. Cell,1985,41(2):497-507.
[71]GENIN P, BRAGANCA J, DARRACQ N, DOLY J, CIVAS A. A novel PRD I and TG binding activity involved in virus-induced transcription of IFN-A genes [J]. Nucleic acids research,1995, 23(24):5055-63.
[72]HONDA K, YANAI H, TAKAOKA A, TANIGUCHI T. Regulation of the type I IFN induction:a current view [J]. International immunology,2005,17(11):1367-78.
[73]GHOSH S, KARIN M. Missing pieces in the NF-kappaB puzzle [J]. Cell,2002,109 Suppl(S81-96.
[74]HACKER H, KARIN M. Regulation and function of IKK and IKK-related kinases [J]. Science's STKE:signal transduction knowledge environment,2006,2006(357):re13.
[75]CHIU Y H, ZHAO M, CHEN Z J. Ubiquitin in NF-kappaB signaling [J]. Chemical reviews,2009, 109(4):1549-60.
[76]LIU P, LI K, GAROFALO R P, BRASIER A R. Respiratory syncytial virus induces RelA release from cytoplasmic 100-kDa NF-kappa B2 complexes via a novel retinoic acid-inducible gene-I{ middle dot}NF-kappa B-inducing kinase signaling pathway [J]. The Journal of biological chemistry,2008. 283(34):23169-78.
[77]TAMURA T, YANAI H, SAVITSKY D, TANIGUCHI T. The IRF family transcription factors in immunity and oncogenesis [J]. Annual review of immunology,2008,26(535-84.
[78]HISCOTT J. Triggering the innate antiviral response through IRF-3 activation [J]. The Journal of biological chemistry,2007,282(21):15325-9.
[79]HONDA K, YANAI H, NEGISHI H, ASAGIRI M. SATO M, MIZUTANI T, SHIMADA N, OHBA Y, TAKAOKA A, YOSHIDA N, TANIGUCHI T. IRF-7 is the master regulator of type-I interferon-dependent immune responses [J]. Nature,2005,434(7034):112-1.
[80]APOSTOLOU E, THANOS D. Virus Infection Induces NF-kappaB-dependent interchromosomal associations mediating monoallelic IFN-beta gene expression [J]. Cell,2008,134(1):85-96.
[81]ALEXOPOULOU L, HOLT A C, MEDZHITOV R, FLAVELL R A. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3 [J]. Nature,2001,413(6857): 732-8.
[82]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. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway [J]. Nature immunology,2003,4(5):491-6.
[83]HORNG T, BARTON G M, MEDZHITOV R. TIRAP:an adapter molecule in the Toll signaling pathway [J]. Nature immunology,2001,2(9):835-41.
[84]OSHIUMI H, MATSUMOTO M, FUNAMI K, AKAZAWA T, SEYA T. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction [J]. Nature immunology,2003,4(2):161-7.
[85]YAMAMOTO M, SATO S, HEMMI H, UEMATSU S, HOSHINO K, KAISHO T, TAKEUCHI O, TAKEDA K, AKIRA S. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway [J]. Nature immunology,2003,4(11):1144-50.
[86]YAMAMOTO M, SATO S, HEMMI H, HOSHINO K, KAISHO T, SANJO H, TAKEUCHI O, SUGIYAMA M, OKABE M, TAKEDA K, AKIRA S. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway [J]. Science,2003,301(5633):640-3.
[87]OSHIUMI H, SASAI M, SHIDA K, FUJITA T, MATSUMOTO M, SEYA T. TIR-containing adapter molecule (TICAM)-2, a bridging adapter recruiting to toll-like receptor 4 TICAM-1 that induces interferon-beta [J]. The Journal of biological chemistry,2003,278(50):49751-62.
[88]CARTY M, GOODBODY R, SCHRODER M, STACK J, MOYNAGH P N, BOWIE A G. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling [J]. Nature immunology,2006,7(10):1074-81.
[89]TROUTMAN T D, HU W, FULENCHEK S, YAMAZAKI T, KUROSAKI T, BAZAN J F, PASARE C. Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt [J]. Proceedings of the National Academy of Sciences of the United States of America,2012,109(1):273-8.
[90]COVERT M W, LEUNG T H, GASTON J E, BALTIMORE D. Achieving stability of lipopolysaccharide-induced NF-kappaB activation [J]. Science,2005,309(5742):1854-7.
[91]WERNER S L, BARKEN D, HOFFMANN A. Stimulus specificity of gene expression programs determined by temporal control of IKK activity [J]. Science,2005,309(5742):1857-61.
[92]TABETA K, HOEBE K, JANSSEN E M, DU X, GEORGEL P, CROZAT K, MUDD S, MANN N, SOVATH S, GOODE J, SHAMEL L, HERSKOVITS A A, PORTNOY D A, COOKE M, TARANTINO L M, WILTSHIRE T, STEINBERG B E, GRINSTEIN S, BEUTLER B. The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3,7 and 9 [J]. Nature immunology,2006,7(2):156-64.
[93]KAWAI T, TAKAHASHI K, SATO S, COBAN C, KUMAR H, KATO H, ISHII K J, TAKEUCHI O, AKIRA S. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type Ⅰ interferon induction [J]. Nature immunology,2005,6(10):981-8.
[94]MEYLAN E, CURRAN J, HOFMANN K, MORADPOUR D, BINDER M, BARTENSCHLAGER R, TSCHOPP J. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus [J]. Nature,2005,437(7062):1167-72.
[95]SETH R B, SUN L, EA C K, CHEN Z J. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3 [J]. Cell,2005,122(5): 669-82.
[96]XU L G, WANG Y Y, HAN K J, LI L Y, ZHAI Z, SHU H B. VISA is an adapter protein required for virus-triggered IFN-beta signaling [J]. Molecular cell,2005,19(6):727-40.
[97]TAY S, DICKMANN L, DIXIT V, ISOHERRANEN N. A comparison of the roles of peroxisome proliferator-activated receptor and retinoic acid receptor on CYP26 regulation [J]. Molecular pharmacology,2010,77(2):218-27.
[98]SUN Q, SUN L, LIU H H, CHEN X, SETH R B, FORMAN J, CHEN Z J. The specific and essential role of MAVS in antiviral innate immune responses [J]. Immunity,2006,24(5):633-42.
[99]ISHIKAWA H, BARBER G N. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling [J]. Nature,2008,455(7213):674-8.
[100]SUN W, LI Y, CHEN L, CHEN H, YOU F, ZHOU X, ZHOU Y, ZHAI Z, CHEN D, JIANG Z. ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization [J]. Proceedings of the National Academy of Sciences of the United States of America, 2009,106(21):8653-8.
[101]JIN L, HILL K K, FILAK H, MOGAN J, KNOWLES H. ZHANG B, PERRAUD A L, CAMBIER J C, LENZ L L. MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP [J]. J Immunol,2011,187(5):2595-601.
[102]CHEN H, SUN H, YOU F, SUN W, ZHOU X, CHEN L, YANG J, WANG Y, TANG H, GUAN Y, XIA W, GU J, ISHIKAWA H, GUTMAN D, BARBER G, QIN Z, JIANG Z. Activation of STAT6 by STING is critical for antiviral innate immunity [J]. Cell,2011,147(2):436-46.
[103]SHIM J H, XIAO C, PASCHAL A E, BAILEY S T, RAO P, HAYDEN M S, LEE K Y, BUSSEY C, STECKEL M, TANAKA N, YAMADA G, AKIRA S, MATSUMOTO K, GHOSH S. TAK1, but not TAB] or TAB2, plays an essential role in multiple signaling pathways in vivo [J]. Genes & development,2005,19(22):2668-81.
[104]KANAYAMA A, SETH R B, SUN L, EA C K, HONG M, SHAITO A, CHIU Y H, DENG L, CHEN Z J. TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains [J]. Molecular cell,2004,15(4):535-48.
[105]LI Q, YAN J, MAO A P, LI C, RAN Y, SHU H B, WANG Y Y. Tripartite motif 8 (TRIMS) modulates TNFalpha-and IL-l beta-triggered NF-kappaB activation by targeting TAK1 for K63-linked polyubiquitination [J]. Proceedings of the National Academy of Sciences of the United States of America,2011,108(48):19341-6.
[106]DIDONATO J A, HAYAKAWA M, ROTHWARF D M, ZANDI E, KARIN M. A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB [J]. Nature,1997, 388(6642):548-54.
[107]ZANDI E, ROTHWARF D M. DELHASE M, HAYAKAWA M, KARIN M. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation [J]. Cell,1997,91(2):243-52.
[108]ROTHWARF D M, ZANDI E, NATOLI G, KARIN M. IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex [J]. Nature,1998,395(6699):297-300.
[109]YAMAOKA S, COURTOIS G, BESSIA C, WHITESIDE S T, WEIL R, AGOU F, KIRK H E, KAY R J, ISRAEL A. Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation [J]. Cell,1998,93(7):1231-40.
[110]ZANDI E, CHEN Y, KARIN M. Direct phosphorylation of IkappaB by IKKalpha and IKKbeta:discrimination between free and NF-kappaB-bound substrate [J]. Science,1998,281(5381): 1360-3.
[111]PAPATRIANTAFYLLOU M. Cell signalling:The NEMO guide to IkappaB [J]. Nature reviews Molecular cell biology,2012,13(7):408.
[112]WANG Y Y, RAN Y, SHU H B. Linear ubiquitination of NEMO brakes the antiviral response [J]. Cell host & microbe,2012,12(2):129-31.
[113]HEMMI H, TAKEUCHI O, SATO S, YAMAMOTO M, KAISHO T, SANJO H, KAWAI T, HOSHINO K, TAKEDA K, AKIRA S. The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection [J]. The Journal of experimental medicine,2004,199(12):1641-50.
[114]PERRY A K, CHOW E K, GOODNOUGH J B, YEH W C, CHENG G. Differential requirement for TANK-binding kinase-1 in type I interferon responses to toll-like receptor activation and viral infection [J]. The Journal of experimental medicine,2004,199(12):1651-8.
[115]TENOEVER B R, NG S L, CHUA M A, MCWHIRTER S M, GARCIA-SASTRE A, MANIATIS T. Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity [J]. Science,2007,315(5816):1274-8.
[116]CHOE J, KELKER M S, WILSON I A. Crystal structure of human toll-like receptor 3 (TLR3) ectodomain [J]. Science,2005,309(5734):581-5.
[117]WEN W, LIU W, YAN J, ZHANG M. Structure basis and unconventional lipid membrane binding properties of the PH-C1 tandem of rho kinases [J]. The Journal of biological chemistry,2008, 283(38):26263-73.
[118]ERMOLAEVA M A, MICHALLET M C, PAPADOPOULOU N, UTERMOHLEN O, KRANIDIOTI K, KOLLIAS G, TSCHOPP J, PASPARAKIS M. Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses [J]. Nature immunology,2008,9(9):1037-46.
[119]POBEZINSKAYA Y L, KIM Y S, CHOKSI S, MORGAN M J, LI T, LIU C, LIU Z. The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent Toll-like receptors [J]. Nature immunology,2008,9(9):1047-54.
[120]TAKEUCHI O, AKIRA S. Pattern recognition receptors and inflammation [J]. Cell,2010. 140(6):805-20.
[121]MANCUSO G, GAMBUZZA M, MIDIRI A, BIONDO C, PAPASERGI S, AKIRA S, TETI G, BENINATI C. Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells [J]. Nature immunology,2009,10(6):587-94.
[122]SANJUAN M A, MILASTA S, GREEN D R. Toll-like receptor signaling in the lysosomal pathways [J]. Immunological reviews,2009,227(1):203-20.
[123]HAAS T, METZGER J, SCHMITZ F, HEIT A. MULLER T, LATZ E, WAGNER H. The DNA sugar backbone 2' deoxyribose determines toll-like receptor 9 activation [J]. Immunity,2008, 28(3):315-23.
[124]HOSHINO K, SUGIYAMA T, MATSUMOTO M, TANAKA T, SAITO M, HEMMI H, OHARA O, AKIRA S, KAISHO T. IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9 [J]. Nature,2006,440(7086):949-53.
[125]UEMATSU S, SATO S, YAMAMOTO M, HIROTANI T, KATO H, TAKESHITA F, MATSUDA M, COBAN C. ISHII K J, KAWAI T, TAKEUCHI O, AKIRA S. Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7-and TLR9-mediated interferon-{alpha} induction [J]. The Journal of experimental medicine,2005,201(6):915-23.
[126]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. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6 [J]. Nature,2006, 439(7073):204-7.
[127]OGANESYAN G, SAHA S K, GUO B, HE J Q, SHAHANGIAN A, ZARNEGAR B, PERRY A, CHENG G. Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response [J]. Nature,2006,439(7073):208-11.
[128]SHINOHARA M L, LU L, BU J, WERNECK M B, KOBAYASHI K S, GLIMCHER L H, CANTOR H. Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells [J]. Nature immunology,2006,7(5):498-506.
[129]JOUNAI N, TAKESHITA F, KOBI YAM A K, S AWANO A, MIYAWAKI A, XIN K Q, ISHII K J, KAWAI T, AKIRA S, SUZUKI K, OKUDA K. The Atg5 Atg12 conjugate associates with innate antiviral immune responses [J]. Proceedings of the National Academy of Sciences of the United States of America,2007,104(35):14050-5.
[130]SAITO T, HIRAI R, LOO Y M, OWEN D, JOHNSON C L, SINHA S C, AKIRA S, FUJITA T, GALE M, JR. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2 [J]. Proceedings of the National Academy of Sciences of the United States of America,2007, 104(2):582-7.
[131]DIAO F, LI S, TIAN Y, ZHANG M, XU L G, ZHANG Y, WANG R P, CHEN D, ZHAI Z, ZHONG B, TIEN P, SHU H B. Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase [J]. Proceedings of the National Academy of Sciences of the United States of America,2007,104(28):11706-11.
[132]MOORE C B, BERGSTRALH D T, DUNCAN J A, LEI Y, MORRISON T E, ZIMMERMANN A G, ACCAVITTI-LOPER M A, MADDEN V J, SUN L, YE Z, LICH J D, HEISE M T, CHEN Z, TING J P. NLRX1 is a regulator of mitochondrial antiviral immunity [J]. Nature,2008, 451(7178):573-7.
[133]HUANG J, LIU T, XU L G, CHEN D, ZHAI Z, SHU H B. SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways [J]. The EMBO journal,2005,24(23):4018-28.
[134]YU Y, HAYWARD G S. The ubiquitin E3 ligase RAUL negatively regulates type i interferon through ubiquitination of the transcription factors IRF7 and IRF3 [J]. Immunity,2010,33(6):863-77.
[135]GACK M U, SHIN Y C, JOO C H, URANO T, LIANG C. SUN L, TAKEUCHI O, AKIRA S, CHEN Z, INOUE S,JUNG J U. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity [J]. Nature,2007,446(7138):916-20.
[136]VALLABHAPURAPU S, MATSUZAWA A, ZHANG W, TSENG P H, KEATS J J, WANG H, VIGNALI D A, BERGSAGEL P L, KARIN M. Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling [J]. Nature immunology,2008,9(12):1364-70.
[137]ZARNEGAR B J, WANG Y, MAHONEY D J, DEMPSEY P W, CHEUNG H H, HE J, SHIBA T, YANG X, YEH W C, MAK T W, KORNELUK R G, CHENG G. Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK [J]. Nature immunology,2008,9(12):1371-8.
[138]MAO A P, LI S, ZHONG B, LI Y, YAN J, LI Q, TENG C, SHU H B. Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for induction of interferon-beta (IFN-beta) and cellular antiviral response [J]. The Journal of biological chemistry,2010,285(13):9470-6.
[139]SPIES B, HOCHREIN H, VABULAS M, HUSTER K, BUSCH D H, SCHMITZ F, HEIT A, WAGNER H. Vaccination with plasmid DNA activates dendritic cells via Toll-like receptor 9 (TLR9) but functions in TLR9-deficient mice [J]. J Immunol,2003,171(11):5908-12.
[140]HEIT A, MAURER T, HOCHREIN H, BAUER S, HUSTER K M, BUSCH D H, WAGNER H. Cutting edge:Toll-like receptor 9 expression is not required for CpG DNA-aided cross-presentation of DNA-conjugated antigens but essential for cross-priming of CD8 T cells [J]. J Immunol,2003, 170(6):2802-5.
[141]STETSON D B, MEDZHITOV R. Recognition of cytosolic DNA activates an IRF3-dependent innate immune response [J]. Immunity,2006,24(1):93-103.
[142]SAITOH T, FUJITA N, YOSHIMORI T, AKIRA S. Regulation of dsDNA-induced innate immune responses by membrane trafficking [J]. Autophagy,2010,6(3):430-2.
[143]WANG Y Y, LIU L J, ZHONG B, LIU T T, LI Y, YANG Y, RAN Y, LI S, TIEN P, SHU H B. WDR5 is essential for assembly of the VISA-associated signaling complex and virus-triggered IRF3 and NF-kappaB activation [J]. Proceedings of the National Academy of Sciences of the United States of America,2010,107(2):815-20.
[144]LIU H M, LOO Y M, HORNER S M, ZORNETZER G A, KATZE M G, GALE M, JR. The mitochondrial targeting chaperone 14-3-3epsilon regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity [J]. Cell host & microbe,2012,11(5):528-37.
[145]RAMAGE R, GREEN J, MUIR T W, OGUNJOBI O M, LOVE S, SHAW K. Synthetic, structural and biological studies of the ubiquitin system:the total chemical synthesis of ubiquitin [J]. The Biochemical journal,1994,299 (Pt 1)(151-8.
[146]OGUNJOBI O, RAMAGE R. Ubiquitin:preparative chemical synthesis, purification and characterization [J]. Biochemical Society transactions,1990,18(6):1322-3.
[147]KERSCHER O, FELBERBAUM R, HOCHSTRASSER M. Modification of proteins by ubiquitin and ubiquitin-like proteins [J]. Annual review of cell and developmental biology,2006, 22(159-80.
[148]PICKART C M, FUSHMAN D. Polyubiquitin chains:polymeric protein signals [J]. Current opinion in chemical biology,2004,8(6):610-6.
[149]IKEDA F, DIKIC I. Atypical ubiquitin chains:new molecular signals.'Protein Modifications: Beyond the Usual Suspects' review series [J]. EMBO reports,2008,9(6):536-42.
[150]MATSUMOTO M L, WICKLIFFE K E, DONG K C, YU C, BOSANAC I, BUSTOS D, PHU L, KIRKPATRICK D S, HYMOWITZ S G, RAPE M, KELLEY R F, DIXIT V M. K11-linked polyubiquitination in cell cycle control revealed by a K11 linkage-specific antibody [J]. Molecular cell, 2010,39(3):477-84.
[151]IKEDA H, KERPPOLA T K. Lysosomal localization of ubiquitinated Jun requires multiple determinants in a lysine-27-linked polyubiquitin conjugate [J]. Molecular biology of the cell,2008, 19(11):4588-601.
[152]CHASTAGNER P, ISRAEL A, BROU C. AIP4/Itch regulates Notch receptor degradation in the absence of ligand [J]. PloS one,2008,3(7):e2735.
[153]MALYNN B A, MA A. Ubiquitin makes its mark on immune regulation [J]. Immunity,2010, 33(6):843-52.
[154]LIU S, CHEN Z J. Expanding role of ubiquitination in NF-kappaB signaling [J]. Cell research,2011,21(1):6-21.
[155]HERSHKO A, CIECHANOVER A. The ubiquitin system [J]. Annual review of biochemistry, 1998,67(425-79.
[156]MCGRATH J P, JENTSCH S, VARSHAVSKY A. UBA 1:an essential yeast gene encoding ubiquitin-activating enzyme [J]. The EMBO journal,1991,10(1):227-36.
[157]MICHALEK M T, GRANT E P, GRAMM C, GOLDBERG A L, ROCK K L. A role for the ubiquitin-dependent proteolytic pathway in MHC class I-restricted antigen presentation [J]. Nature, 1993,363(6429):552-4.
[158]PICKART C M. Mechanisms underlying ubiquitination [J]. Annual review of biochemistry, 2001,70(503-33.
[159]HOFMANN R M, PICKART C M. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair [J]. Cell,1999,96(5): 645-53.
[160]DENG L, WANG C, SPENCER E, YANG L, BRAUN A, YOU J, SLAUGHTER C, PICKART C, CHEN Z J. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain [J]. Cell,2000,103(2): 351-61.
[161]LIU Y C. Ubiquitin ligases and the immune response [J]. Annual review of immunology, 2004,22(81-127.
[162]HUIBREGTSE J M, SCHEFFNER M, BEAUDENON S, HOWLEY P M. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase [J]. Proceedings of the National Academy of Sciences of the United States of America,1995,92(7):2563-7.
[163]SCHEFFNER M, NUBER U, HUIBREGTSE J M. Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade [J]. Nature,1995,373(6509):81-3.
[164]FREEMONT P S. RING for destruction? [J]. Current biology:CB.2000,10(2):R84-7.
[165]JOAZEIRO C A, WEISSMAN A M. RING finger proteins:mediators of ubiquitin ligase activity [J]. Cell,2000,102(5):549-52.
[166]PERTEL T, HAUSMANN S, MORGER D, ZUGER S, GUERRA J, LASCANO J, REINHARD C, SANTONI F A, UCHIL P D, CHATEL L, BISIAUX A, ALBERT M L, STRAMBIO-DE-CASTILLIA C, MOTHES W, PIZZATO M, GRUTTER M G, LUBAN J. TRIM5 is an innate immune sensor for the retrovirus capsid lattice [J]. Nature,2011,472(7343):361-5.
[167]YANG K, SHI H X, LIU X Y, SHAN Y F, WEI B, CHEN S, WANG C. TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response [J]. J Immunol,2009,182(6): 3782-92.
[168]HIGGS R, NI GABHANN J, BEN LARBI N, BREEN E P, FITZGERALD K A, JEFFERIES C A. The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3 [J]. J Immunol,2008,181(3): 1780-6.
[169]HIGGS R, LAZZARI E, WYNNE C, NI GABHANN J, ESPINOSA A, WAHREN-HERLENIUS M, JEFFERIES C A. Self protection from anti-viral responses-Ro52 promotes degradation of the transcription factor IRF7 downstream of the viral Toll-Like receptors [J]. PloS one,2010,5(7):e11776.
[170]YOUNG J A, SERMWITTAYAWONG D, KIM H J, NANDU S, AN N, ERDJUMENT-BROMAGE H, TEMPST P, COSCOY L, WINOTO A. Fas-associated death domain (FADD) and the E3 ubiquitin-protein ligase TRIM21 interact to negatively regulate virus-induced interferon production [J]. The Journal of biological chemistry,2011,286(8):6521-31.
[171]ZHANG Z, BAO M, LU N, WENG L, YUAN B, LIU Y J. The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA [J]. Nature immunology,2013,14(2):172-8.
[172]ARIMOTO K, FUNAMI K, SAEKI Y, TANAKA K, OKAWA K, TAKEUCHI O, AKIRA S, MURAKAMI Y, SHIMOTOHNO K. Polyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense [J]. Proceedings of the National Academy of Sciences of the United States of America,2010,107(36):15856-61.
[173]POOLE E, GROVES I, MACDONALD A, PANG Y, ALCAMI A, SINCLAIR J. Identification of TRIM23 as a cofactor involved in the regulation of NF-kappaB by human cytomegalovirus [J]. Journal of virology,2009,83(8):3581-90.
[174]GACK M U, ALBRECHT R A, URANO T, INN K S, HUANG I C, CARNERO E, FARZAN M, INOUE S, JUNG J U, GARCIA-SASTRE A. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I [J]. Cell host & microbe,2009, 5(5):439-49.
[175]TSUCHIDA T, ZOU J, SAITOH T, KUMAR H, ABE T, MATSUURA Y, KAWAI T, AKIRA S. The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA [J]. Immunity,2010,33(5):765-76.
[176]OUYANG S, SONG X, WANG Y, RU H, SHAW N, JIANG Y, NIU F, ZHU Y, QIU W, PARVATIYAR K, LI Y, ZHANG R, CHENG G, LIU Z J. Structural analysis of the STING adaptor protein reveals a hydrophobic dimer interface and mode of cyclic di-GMP binding [J]. Immunity,2012, 36(6):1073-86.
[177]ZHAO W, WANG L, ZHANG M, YUAN C, GAO C. E3 ubiquitin ligase tripartite motif 38 negatively regulates TLR-mediated immune responses by proteasomal degradation of TNF receptor-associated factor 6 in macrophages [J]. J Immunol,2012,188(6):2567-74.
[178]ZHAO W, WANG L, ZHANG M, WANG P, YUAN C, QI J, MENG H, GAO C. Tripartite motif-containing protein 38 negatively regulates TLR3/4- and RIG-I-mediated IFN-beta production and antiviral response by targeting NAP1 [J]. J Immunol,2012,188(11):5311-8.
[179]XUE Q, ZHOU Z, LEI X, LIU X, HE B, WANG J, HUNG T. TRIM38 negatively regulates TLR3-MEdiated IFN-beta signaling by targeting TRIF for degradation [J]. PloS one,2012,7(10): e46825.
[180]ZHONG B, ZHANG L, LEI C, LI Y, MAO A P, YANG Y, WANG Y Y, ZHANG X L, SHU H B. The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA [J]. Immunity,2009,30(3):397-407.
[181]ZHONG B, ZHANG Y, TAN B, LIU T T, WANG Y Y, SHU H B. The E3 ubiquitin ligase RNF5 targets virus-induced signaling adaptor for ubiquitination and degradation [J]. J Immunol,2010, 184(11):6249-55.
[182]YOU F, SUN H, ZHOU X, SUN W, LIANG S, ZHAI Z, JIANG Z. PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4 [J]. Nature immunology,2009, 10(12):1300-8.
[183]ARIMOTO K, TAKAHASHI H, HISHIKI T, KONISHI H, FUJITA T, SHIMOTOHNO K. Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125 [J]. Proceedings of the National Academy of Sciences of the United States of America,2007,104(18):7500-5.
[184]GAO D, YANG Y K, WANG R P, ZHOU X, DIAO F C, LI M D, ZHAI Z H, JIANG Z F, CHEN D Y. REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-Ⅰ [J]. PloS one,2009,4(6):e5760.
[185]OSHIUMI H, MIYASHITA M, INOUE N, OKABE M, MATSUMOTO M, SEYA T. The ubiquitin ligase Riplet is essential for RIG-1-dependent innate immune responses to RNA virus infection [J]. Cell host & microbe,2010,8(6):496-509.
[186]NAKHAEI P, MESPLEDE T, SOLIS M, SUN Q, ZHAO T, YANG L, CHUANG T H, WARE C F, LIN R, HISCOTT J. The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS signaling pathway by targeting TRAF3 for degradation [J]. PLoS pathogens,2009,5(11): e1000650.
[187]CUI J, LI Y, ZHU L, LIU D, SONG YANG Z, WANG H Y, WANG R F. NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4 [J]. Nature immunology,2012,13(4):387-95.
[188]LI S, WANG L, BERMAN M, KONG Y Y, DORF M E. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production [J]. Immunity,2011,35(3): 426-40.
[189]ZHANG M, TIAN Y, WANG R P, GAO D, ZHANG Y, DIAO F C, CHEN D Y, ZHAI Z H, SHU H B. Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3 [J]. Cell research,2008,18(11):1096-104.
[190]MERONI G, DIEZ-ROUX G. TRIM/RBCC, a novel class of'single protein RING finger' E3 ubiquitin ligases [J]. BioEssays:news and reviews in molecular, cellular and developmental biology, 2005,27(11):1147-57.
[191]OZATO K, SHIN D M, CHANG T H, MORSE H C,3RD. TRIM family proteins and their emerging roles in innate immunity [J]. Nature reviews Immunology,2008,8(11):849-60.
[192]SARDIELLO M, CAIRO S, FONTANELLA B, BALLABIO A, MERONI G. Genomic analysis of the TRIM family reveals two groups of genes with distinct evolutionary properties [J]. BMC evolutionary biology,2008,8(225.
[193]SHORT K M, COX T C. Subclassification of the RBCC/TRIM superfamily reveals a novel motif necessary for microtubule binding [J]. The Journal of biological chemistry,2006,281(13): 8970-80.
[194]VERSTEEG G A, RAJSBAUM R, SANCHEZ-APARICIO M T, MAESTRE A M. VALDIVIEZO J, SHI M, INN K S, FERNANDEZ-SESMA A, JUNG J, GARCTA-SASTRE A. The E3-Ligase TRIM Family of Proteins Regulates Signaling Pathways Triggered by Innate Immune Pattern-Recognition Receptors [J]. Immunity,2013,38(2):384-98.
[195]KAWAI T, AKIRA S. Regulation of innate immune signalling pathways by the tripartite motif (TRIM) family proteins [J]. EMBO molecular medicine,2011,3(9):513-27.
[196]SHEN Y, LI N L, WANG J, LIU B, LESTER S, LI K. TRIM56 is an essential component of the TLR3 antiviral signaling pathway [J]. The Journal of biological chemistry,2012,287(43): 36404-13.
[197]LIANG Q, DENG H, LI X, WU X, TANG Q, CHANG T H, PENG H, RAUSCHER F J, 3RD, OZATO K, ZHU F. Tripartite motif-containing protein 28 is a small ubiquitin-related modifier E3 ligase and negative regulator of IFN regulatory factor 7 [J]. J Immunol,2011,187(9):4754-63.
[198]ZHA J, HAN K J, XU L G, HE W, ZHOU Q, CHEN D, ZHAI Z, SHU H B. The Ret finger protein inhibits signaling mediated by the noncanonical and canonical IkappaB kinase family members [J]. J Immunol,2006,176(2):1072-80.
[199]SHI M, DENG W, BI E, MAO K, JI Y, LIN G, WU X, TAO Z, LI Z, CAI X, SUN S, XIANG C, SUN B. TRIM30 alpha negatively regulates TLR-mediated NF-kappa B activation by targeting TAB2 and TAB3 for degradation [J]. Nature immunology,2008,9(4):369-77.
[200]LOCKE M, TINSLEY C L, BENSON M A, BLAKE D J. TRIM32 is an E3 ubiquitin ligase for dysbindin [J]. Human molecular genetics,2009,18(13):2344-58.
[201]KUDRYASHOVA E, KUDRYASHOV D, KRAMEROVA I, SPENCER M J. Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2H that binds to skeletal muscle myosin and ubiquitinates actin [J]. Journal of molecular biology,2005,354(2):413-24.
[202]ALBOR A, EL-HIZAWI S, HORN E J, LAEDERICH M, FROSK P, WROGEMANN K, KULESZ-MARTIN M. The interaction of Piasy with Trim32, an E3-ubiquitin ligase mutated in limb-girdle muscular dystrophy type 2H, promotes Piasy degradation and regulates UVB-induced keratinocyte apoptosis through NFkappaB [J]. The Journal of biological chemistry,2006,281(35): 25850-66.
[203]KANO S, MIYAJIMA N, FUKUDA S, HATAKEYAMA S. Tripartite motif protein 32 facilitates cell growth and migration via degradation of Abl-interactor 2 [J]. Cancer research,2008, 68(14):5572-80.
[204]SCHWAMBORN J C, BEREZIKOV E, KNOBLICH J A. The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors [J]. Cell,2009,136(5): 913-25.
[205]KUDRYASHOVA E, STRUYK A, MOKHONOVA E, CANNON S C, SPENCER M J. The common missense mutation D489N in TRIM32 causing limb girdle muscular dystrophy 2H leads to loss of the mutated protein in knock-in mice resulting in a Trim32-null phenotype [J]. Human molecular genetics,2011,20(20):3925-32.
[206]HORN E J, ALBOR A, LIU Y, EL-HIZAWI S, VANDERBEEK G E, BABCOCK M, BOWDEN G T, HENNINGS H, LOZANO G, WEINBERG W C, KULESZ-MARTIN M. RING protein Trim32 associated with skin carcinogenesis has anti-apoptotic and E3-ubiquitin ligase properties [J]. Carcinogenesis,2004,25(2):157-67.
[207]LIU Y, LAGOWSKI J P, GAO S, RAYMOND J H, WHITE C R, KULESZ-MARTIN M F. Regulation of the psoriatic chemokine CCL20 by E3 ligases Trim32 and Piasy in keratinocytes [J]. The Journal of investigative dermatology,2010,130(5):1384-90.
[208]KUDRYASHOVA E, WU J, HAVTON L A, SPENCER M J. Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component [J]. Human molecular genetics,2009,18(7):1353-67.
[209]NICKLAS S, OTTO A, WU X, MILLER P, STELZER S, WEN Y, KUANG S, WROGEMANN K, PATEL K, DING H, SCHWAMBORN J C. TRIM32 regulates skeletal muscle stem cell differentiation and is necessary for normal adult muscle regeneration [J]. PloS one,2012,7(1): e30445.
[2]KLOTMAN M E, CHANG T L. Defensins in innate antiviral immunity [J]. Nature reviews Immunology,2006,6(6):447-56.
[3]NATHAN C. Neutrophils and immunity:challenges and opportunities [J]. Nature reviews Immunology,2006,6(3):173-82.
[4]BIRON C A, NGUYEN K B, PIEN G C, COUSENS L P, SALAZAR-MATHER T P. Natural killer cells in antiviral defense:function and regulation by innate cytokines [J]. Annual review of immunology,1999,17(189-220.
[5]CARROLL M C. The role of complement and complement receptors in induction and regulation of immunity [J]. Annual review of immunology,1998,16(545-68.
[6]LARSEN G L, HENSON P M. Mediators of inflammation [J]. Annual review of immunology, 1983,1(335-59.
[7]BEUTLER B, CERAMI A. The biology of cachectin/TNF-a primary mediator of the host response [J]. Annual review of immunology,1989,7(625-55.
[8]ISAACS A, LINDENMANN J. Virus interference. I. The interferon [J]. Proc R Soc Lond B Biol Sci,1957,147(927):258-67. [9] SADLER A J, WILLIAMS B R. Interferon-inducible antiviral effectors [J]. Nature reviews
Immunology,2008,8(7):559-68.
[10]JANEWAY C A, JR., MEDZHITOV R. Innate immune recognition [J]. Annual review of immunology,2002,20(197-216.
[11]WRIGHT J R. Immunoregulatory functions of surfactant proteins [J]. Nature reviews Immunology,2005,5(1):58-68.
[12]AKIRA S, TAKEDA K. Toll-like receptor signalling [J]. Nature reviews Immunology,2004,4(7): 499-511.
[13]BEUTLER B. Toll-like receptors and their place in immunology. Where does the immune response to infection begin? [J]. Nature reviews Immunology,2004,4(7):498.
[14]MEDZHITOV R. Toll-like receptors and innate immunity [J]. Nature reviews Immunology,2001, 1(2):135-45.
[15]AKIRA S, UEMATSU S, TAKEUCHI O. Pathogen recognition and innate immunity [J]. Cell, 2006,124(4):783-801.
[16]YONEYAMA M, FUJITA T. RNA recognition and signal transduction by RIG-I-like receptors [J]. Immunological reviews,2009,227(1):54-65.
[17]YONEYAMA M, KIKUCHI M, NATSUKAWA T, SHINOBU N, IMAIZUMI T, MIYAGISHI M, TAIRA K, AKIRA S, FUJITA T. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses [J]. Nature immunology,2004,5(7):730-7.
[18]CUI S, EISENACHER K, KIRCHHOFER A, BRZOZKA K, LAMMENS A, LAMMENS K, FUJITA T, CONZELMANN K K, KRUG A, HOPFNER K P. The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I [J]. Molecular cell,2008,29(2):169-79.
[19]TAKAHASI K, YONEYAMA M, NISHIHORI T, HIRAI R, KUMETA H, NARITA R, GALE M. JR., INAGAKI F, FUJITA T. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses [J]. Molecular cell,2008,29(4):428-40.
[20]YONEYAMA M, FUJITA T. Structural mechanism of RNA recognition by the RIG-I-like receptors [J]. Immunity,2008,29(2):178-81.
[21]KANG D C, GOPALKRISHNAN R V, WU Q, JANKOWSKY E, PYLE A M, FISHER P B. mda-5:An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties [J]. Proceedings of the National Academy of Sciences of the United States of America,2002,99(2):637-42.
[22]WU B, PEISLEY A, RICHARDS C, YAO H, ZENG X, LIN C, CHU F, WALZ T, HUR S. Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5 [J]. Cell,2013,152(1-2):276-89.
[23]ROTHENFUSSER S, GOUTAGNY N, DIPERNA G, GONG M, MONKS B G, SCHOENEMEYER A, YAMAMOTO M, AKIRA S, FITZGERALD K A. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I [J]. J Immunol, 2005,175(8):5260-8.
[24]LOO Y M, GALE M, JR. Immune signaling by RIG-I-like receptors [J]. Immunity,2011,34(5): 680-92.
[25]KATO H, TAKEUCHI O, MIKAMO-SATOH E, HIRAI R, KAWAI T, MATSUSHITA K, HIIRAGI A, DERMODY T S, FUJITA T, AKIRA S. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5 [J]. The Journal of experimental medicine,2008,205(7):1601-10.
[26]HORNUNG V, ELLEGAST J, KIM S, BRZOZKA K, JUNG A, KATO H, POECK H, AKIRA S, CONZELMANN K K, SCHLEE M, ENDRES S, HARTMANN G.5'-Triphosphate RNA is the ligand for RIG-I [J]. Science,2006,314(5801):994-7.
[27]PICHLMAIR A, SCHULZ O, TAN C P, NASLUND T I, LILJESTROM P, WEBER F, REIS E SOUSA C. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates [J]. Science,2006,314(5801):997-1001.
[28]SCHLEE M, ROTH A, HORNUNG V, HAGMANN C A, WIMMENAUER V, BARCHET W, COCH C, JANKE M, MIHAILOVIC A, WARDLE G, JURANEK S, KATO H, KAWAI T, POECK H, FITZGERALD K A, TAKEUCHI O, AKIRA S, TUSCHL T, LATZ E, LUDWIG J, HARTMANN G. Recognition of 5'triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus [J]. Immunity,2009,31(1):25-34.
[29]PEISLEY A, LIN C, WU B, ORME-JOHNSON M, LIU M, WALZ T, HUR S. Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition [J]. Proceedings of the National Academy of Sciences of the United States of America,2011,108(52):21010-5.
[30]PEISLEY A, JO M H, LIN C, WU B, ORME-JOHNSON M, WALZ T, HOHNG S, HUR S. Kinetic mechanism for viral dsRNA length discrimination by MDA5 filaments [J]. Proceedings of the National Academy of Sciences of the United States of America,2012,109(49):E3340-9.
[31]YONEYAMA M, KIKUCHI M, MATSUMOTO K, IMAIZUMI T, MIYAGISHI M, TAIRA K, FOY E, LOO Y M, GALE M, JR., AKIRA S, YONEHARA S, KATO A, FUJITA T. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity [J]. J Immunol,2005,175(5):2851-8.
[32]VENKATARAMAN T, VALDES M, ELSBY R, KAKUTA S, CACERES G, SAIJO S, IWAKURA Y, BARBER G N. Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses [J]. J Immunol,2007,178(10):6444-55.
[33]TAKAHASI K, KUMETA H, TSUDUKI N, NARITA R, SHIGEMOTO T, HIRAI R, YONEYAMA M, HORIUCHI M, OGURA K, FUJITA T, INAGAKI F. Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains:identification of the RNA recognition loop in RIG-I-like receptors [J]. The Journal of biological chemistry,2009,284(26):17465-74.
[34]PIPPIG D A, HELLMUTH J C, CUI S, KIRCHHOFER A, LAMMENS K, LAMMENS A, SCHMIDT A, ROTHENFUSSER S, HOPFNER K P. The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA [J]. Nucleic acids research,2009,37(6):2014-25.
[35]SATOH T, KATO H, KUMAGAI Y, YONEYAMA M, SATO S, MATSUSHITA K, TSUJIMURA T, FUJITA T, AKIRA S, TAKEUCHI O. LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses [J]. Proceedings of the National Academy of Sciences of the United States of America,2010,107(4):1512-7.
[36]TAKEUCHI O, AKIRA S. Innate immunity to virus infection [J]. Immunological reviews,2009, 227(1):75-86.
[37]YE Z, TING J P. NLR, the nucleotide-binding domain leucine-rich repeat containing gene family [J]. Current opinion in immunology,2008,20(1):3-9.
[38]FRANCHI L, WARNER N, VIANI K, NUNEZ G. Function of Nod-like receptors in microbial recognition and host defense [J]. Immunological reviews,2009,227(1):106-28.
[39]SHAW M H, REIMER T, KIM Y G, NUNEZ G. NOD-like receptors (NLRs):bona fide intracellular microbial sensors [J]. Current opinion in immunology,2008,20(4):377-82.
[40]SABBAH A, CHANG T H, HARNACK R, FROHLICH V, TOMINAGAK, DUBE P H, XIANG Y, BOSE S. Activation of innate immune antiviral responses by Nod2 [J]. Nature immunology,2009, 10(10):1073-80.
[41]ISHII K J, COBAN C, KATO H, TAKAHASHI K, TORII Y, TAKESHITA F, LUDWIG H, SUTTER G, SUZUKI K, HEMMI H, SATO S, YAMAMOTO M, UEMATSU S, KAWAI T, TAKEUCHI O, AKIRA S. A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA [J]. Nature immunology,2006,7(1):40-8.
[42]ISHII K J, KAWAGOE T, KOYAMA S, MATSUI K, KUMAR H, KAWAI T, UEMATSU S, TAKEUCHI O, TAKESHITA F, COBAN C, AKIRA S. TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines [J]. Nature,2008,451(7179):725-9.
[43]TAKAOKA A, WANG Z, CHOI M K, YANAI H, NEGISHI H, BAN T, LU Y, MIYAGISHI M, KODAMA T, HONDA K, OHBA Y, TANIGUCHI T. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response [J]. Nature,2007,448(7152):501-5.
[44]LIPPMANN J, ROTHENBURG S, DEIGENDESCH N, EITEL J, MEIXENBERGER K, VAN LAAK V, SLEVOGT H, N'GUESSAN P D, HIPPENSTIEL S, CHAKRABORTY T, FLIEGER A, SUTTORP N, OPITZ B. IFNbeta responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI) [J]. Cellular microbiology,2008,10(12): 2579-88.
[45]KAISER W J, UPTON J W, MOCARSKI E S. Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors [J]. J Immunol,2008,181(9):6427-34.
[46]BURCKSTUMMER T, BAUMANN C, BLUML S, DIXIT E, DURNBERGER G, JAHN H, PLANYAVSKY M, BILBAN M, COLINGE J, BENNETT K L, SUPERTI-FURGA G. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome [J]. Nature immunology,2009,10(3):266-72.
[47]FERNANDES-ALNEMRI T, YU J W, DATTA P, WU J, ALNEMRI E S. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA [J]. Nature,2009,458(7237):509-13.
[48]HORNUNG V, ABLASSER A, CHARREL-DENNIS M, BAUERNFEIND F, HORVATH G, CAFFREY D R, LATZ E, FITZGERALD K A. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC [J]. Nature,2009,458(7237):514-8.
[49]ZHONG B, YANG Y, LI S, WANG Y Y, LI Y, DIAO F, LEI C, HE X, ZHANG L, TIEN P, SHU H B. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation [J]. Immunity,2008,29(4):538-50.
[50]ISHIKAWA H, MA Z, BARBER G N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity [J]. Nature,2009,461(7265):788-92.
[51]CHIU Y H, MACMILLAN J B, CHEN Z J. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway [J]. Cell,2009,138(3):576-91.
[52]UNTERHOLZNER L, KEATING S E, BARAN M, HORAN K A, JENSEN S B, SHARMA S, SIROIS C M, JIN T, LATZ E, XIAO T S, FITZGERALD K A, PALUDAN S R, BOWIE A G. IFI16 is an innate immune sensor for intracellular DNA [J]. Nature immunology,2010,11(11):997-1004.
[53]YANG P, AN H, LIU X, WEN M, ZHENG Y, RUI Y, CAO X. The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a beta-catenin-dependent pathway [J]. Nature immunology,2010,11(6):487-94.
[54]KIM T, PAZHOOR S, BAO M, ZHANG Z, HANABUCHI S, FACCHINETTI V, BOVER L, PLUMAS J, CHAPEROT L, QIN J, LIU Y J. Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells [J]. Proceedings of the National Academy of Sciences of the United States of America,2010,107(34): 15181-6.
[55]ZHANG Z, YUAN B, BAO M, LU N, KIM T, LIU Y J. The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells [J]. Nature immunology,2011,12(10):959-65.
[56]PARVATIYAR K, ZHANG Z, TELES R M, OUYANG S, JIANG Y, IYER S S, ZAVER S A, SCHENK M, ZENG S, ZHONG W, LIU Z J, MODLIN R L, LIU Y J, CHENG G. The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response [J]. Nature immunology,2012,13(12):1155-61.
[57]WU J, SUN L, CHEN X, DU F, SHI H, CHEN C, CHEN Z J. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA [J]. Science,2013, 339(6121):826-30.
[58]SUN L, WU J, DU F, CHEN X, CHEN Z J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway [J]. Science,2013,339(6121):786-91.
[59]NIE Y, WANG Y Y. Innate immune responses to DNA viruses [J]. Protein & cell,2013,4(1):1-7.
[60]KAWAI T, AKIRA S. The roles of TLRs, RLRs and NLRs in pathogen recognition [J]. International immunology,2009,21(4):317-37.
[61]THEOFILOPOULOS A N, BACCALA R, BEUTLER B, KONO D H. Type I interferons (alpha/beta) in immunity and autoimmunity [J]. Annual review of immunology,2005,23(307-36.
[62]GRANDVAUX N, SERVANT M J, TENOEVER B, SEN G C, BALACHANDRAN S, BARBER G N, LIN R, HISCOTT J. Transcriptional profiling of interferon regulatory factor 3 target genes:direct involvement in the regulation of interferon-stimulated genes [J]. Journal of virology,2002,76(11): 5532-9.
[63]SAMUEL C E. Antiviral actions of interferons [J]. Clinical microbiology reviews,2001,14(4): 778-809, table of contents.
[64]TANIGUCHI T, MANTEI N, SCHWARZSTEIN M, NAGATA S, MURAMATSU M, WEISSMANN C. Human leukocyte and fibroblast interferons are structurally related [J]. Nature,1980, 285(5766):547-9.
[65]THANOS D, MANIATIS T. Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome [J]. Cell,1995,83(7):1091-100.
[66]WATHELET M G, LIN C H, PAREKH B S, RONCO L V, HOWLEY P M, MANIATIS T. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo [J]. Molecular cell,1998,1(4):507-18.
[67]AGALIOTI T, LOMVARDAS S, PAREKH B, YIE J, MANIATIS T, THANOS D. Ordered recruitment of chromatin modifying and general transcription factors to the IFN-beta promoter [J]. Cell, 2000,103(4):667-78.
[68]HONDA K, TAKAOKA A, TANIGUCHI T. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors [J]. Immunity,2006,25(3):349-60.
[69]RAJ N B, ISRAELI R, KELLUM M, PITHA P M. Upstream regulatory elements of murine alpha 4-interferon gene confer inducibility and cell type-restricted expression [J]. The Journal of biological chemistry,1989,264(19):11149-57.
[70]RYALS J, DIERKS P, RAGG H, WEISSMANN C. A 46-nucleotide promoter segment from an IFN-alpha gene renders an unrelated promoter inducible by virus [J]. Cell,1985,41(2):497-507.
[71]GENIN P, BRAGANCA J, DARRACQ N, DOLY J, CIVAS A. A novel PRD I and TG binding activity involved in virus-induced transcription of IFN-A genes [J]. Nucleic acids research,1995, 23(24):5055-63.
[72]HONDA K, YANAI H, TAKAOKA A, TANIGUCHI T. Regulation of the type I IFN induction:a current view [J]. International immunology,2005,17(11):1367-78.
[73]GHOSH S, KARIN M. Missing pieces in the NF-kappaB puzzle [J]. Cell,2002,109 Suppl(S81-96.
[74]HACKER H, KARIN M. Regulation and function of IKK and IKK-related kinases [J]. Science's STKE:signal transduction knowledge environment,2006,2006(357):re13.
[75]CHIU Y H, ZHAO M, CHEN Z J. Ubiquitin in NF-kappaB signaling [J]. Chemical reviews,2009, 109(4):1549-60.
[76]LIU P, LI K, GAROFALO R P, BRASIER A R. Respiratory syncytial virus induces RelA release from cytoplasmic 100-kDa NF-kappa B2 complexes via a novel retinoic acid-inducible gene-I{ middle dot}NF-kappa B-inducing kinase signaling pathway [J]. The Journal of biological chemistry,2008. 283(34):23169-78.
[77]TAMURA T, YANAI H, SAVITSKY D, TANIGUCHI T. The IRF family transcription factors in immunity and oncogenesis [J]. Annual review of immunology,2008,26(535-84.
[78]HISCOTT J. Triggering the innate antiviral response through IRF-3 activation [J]. The Journal of biological chemistry,2007,282(21):15325-9.
[79]HONDA K, YANAI H, NEGISHI H, ASAGIRI M. SATO M, MIZUTANI T, SHIMADA N, OHBA Y, TAKAOKA A, YOSHIDA N, TANIGUCHI T. IRF-7 is the master regulator of type-I interferon-dependent immune responses [J]. Nature,2005,434(7034):112-1.
[80]APOSTOLOU E, THANOS D. Virus Infection Induces NF-kappaB-dependent interchromosomal associations mediating monoallelic IFN-beta gene expression [J]. Cell,2008,134(1):85-96.
[81]ALEXOPOULOU L, HOLT A C, MEDZHITOV R, FLAVELL R A. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3 [J]. Nature,2001,413(6857): 732-8.
[82]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. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway [J]. Nature immunology,2003,4(5):491-6.
[83]HORNG T, BARTON G M, MEDZHITOV R. TIRAP:an adapter molecule in the Toll signaling pathway [J]. Nature immunology,2001,2(9):835-41.
[84]OSHIUMI H, MATSUMOTO M, FUNAMI K, AKAZAWA T, SEYA T. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction [J]. Nature immunology,2003,4(2):161-7.
[85]YAMAMOTO M, SATO S, HEMMI H, UEMATSU S, HOSHINO K, KAISHO T, TAKEUCHI O, TAKEDA K, AKIRA S. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway [J]. Nature immunology,2003,4(11):1144-50.
[86]YAMAMOTO M, SATO S, HEMMI H, HOSHINO K, KAISHO T, SANJO H, TAKEUCHI O, SUGIYAMA M, OKABE M, TAKEDA K, AKIRA S. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway [J]. Science,2003,301(5633):640-3.
[87]OSHIUMI H, SASAI M, SHIDA K, FUJITA T, MATSUMOTO M, SEYA T. TIR-containing adapter molecule (TICAM)-2, a bridging adapter recruiting to toll-like receptor 4 TICAM-1 that induces interferon-beta [J]. The Journal of biological chemistry,2003,278(50):49751-62.
[88]CARTY M, GOODBODY R, SCHRODER M, STACK J, MOYNAGH P N, BOWIE A G. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling [J]. Nature immunology,2006,7(10):1074-81.
[89]TROUTMAN T D, HU W, FULENCHEK S, YAMAZAKI T, KUROSAKI T, BAZAN J F, PASARE C. Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt [J]. Proceedings of the National Academy of Sciences of the United States of America,2012,109(1):273-8.
[90]COVERT M W, LEUNG T H, GASTON J E, BALTIMORE D. Achieving stability of lipopolysaccharide-induced NF-kappaB activation [J]. Science,2005,309(5742):1854-7.
[91]WERNER S L, BARKEN D, HOFFMANN A. Stimulus specificity of gene expression programs determined by temporal control of IKK activity [J]. Science,2005,309(5742):1857-61.
[92]TABETA K, HOEBE K, JANSSEN E M, DU X, GEORGEL P, CROZAT K, MUDD S, MANN N, SOVATH S, GOODE J, SHAMEL L, HERSKOVITS A A, PORTNOY D A, COOKE M, TARANTINO L M, WILTSHIRE T, STEINBERG B E, GRINSTEIN S, BEUTLER B. The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3,7 and 9 [J]. Nature immunology,2006,7(2):156-64.
[93]KAWAI T, TAKAHASHI K, SATO S, COBAN C, KUMAR H, KATO H, ISHII K J, TAKEUCHI O, AKIRA S. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type Ⅰ interferon induction [J]. Nature immunology,2005,6(10):981-8.
[94]MEYLAN E, CURRAN J, HOFMANN K, MORADPOUR D, BINDER M, BARTENSCHLAGER R, TSCHOPP J. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus [J]. Nature,2005,437(7062):1167-72.
[95]SETH R B, SUN L, EA C K, CHEN Z J. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3 [J]. Cell,2005,122(5): 669-82.
[96]XU L G, WANG Y Y, HAN K J, LI L Y, ZHAI Z, SHU H B. VISA is an adapter protein required for virus-triggered IFN-beta signaling [J]. Molecular cell,2005,19(6):727-40.
[97]TAY S, DICKMANN L, DIXIT V, ISOHERRANEN N. A comparison of the roles of peroxisome proliferator-activated receptor and retinoic acid receptor on CYP26 regulation [J]. Molecular pharmacology,2010,77(2):218-27.
[98]SUN Q, SUN L, LIU H H, CHEN X, SETH R B, FORMAN J, CHEN Z J. The specific and essential role of MAVS in antiviral innate immune responses [J]. Immunity,2006,24(5):633-42.
[99]ISHIKAWA H, BARBER G N. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling [J]. Nature,2008,455(7213):674-8.
[100]SUN W, LI Y, CHEN L, CHEN H, YOU F, ZHOU X, ZHOU Y, ZHAI Z, CHEN D, JIANG Z. ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization [J]. Proceedings of the National Academy of Sciences of the United States of America, 2009,106(21):8653-8.
[101]JIN L, HILL K K, FILAK H, MOGAN J, KNOWLES H. ZHANG B, PERRAUD A L, CAMBIER J C, LENZ L L. MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP [J]. J Immunol,2011,187(5):2595-601.
[102]CHEN H, SUN H, YOU F, SUN W, ZHOU X, CHEN L, YANG J, WANG Y, TANG H, GUAN Y, XIA W, GU J, ISHIKAWA H, GUTMAN D, BARBER G, QIN Z, JIANG Z. Activation of STAT6 by STING is critical for antiviral innate immunity [J]. Cell,2011,147(2):436-46.
[103]SHIM J H, XIAO C, PASCHAL A E, BAILEY S T, RAO P, HAYDEN M S, LEE K Y, BUSSEY C, STECKEL M, TANAKA N, YAMADA G, AKIRA S, MATSUMOTO K, GHOSH S. TAK1, but not TAB] or TAB2, plays an essential role in multiple signaling pathways in vivo [J]. Genes & development,2005,19(22):2668-81.
[104]KANAYAMA A, SETH R B, SUN L, EA C K, HONG M, SHAITO A, CHIU Y H, DENG L, CHEN Z J. TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains [J]. Molecular cell,2004,15(4):535-48.
[105]LI Q, YAN J, MAO A P, LI C, RAN Y, SHU H B, WANG Y Y. Tripartite motif 8 (TRIMS) modulates TNFalpha-and IL-l beta-triggered NF-kappaB activation by targeting TAK1 for K63-linked polyubiquitination [J]. Proceedings of the National Academy of Sciences of the United States of America,2011,108(48):19341-6.
[106]DIDONATO J A, HAYAKAWA M, ROTHWARF D M, ZANDI E, KARIN M. A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB [J]. Nature,1997, 388(6642):548-54.
[107]ZANDI E, ROTHWARF D M. DELHASE M, HAYAKAWA M, KARIN M. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation [J]. Cell,1997,91(2):243-52.
[108]ROTHWARF D M, ZANDI E, NATOLI G, KARIN M. IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex [J]. Nature,1998,395(6699):297-300.
[109]YAMAOKA S, COURTOIS G, BESSIA C, WHITESIDE S T, WEIL R, AGOU F, KIRK H E, KAY R J, ISRAEL A. Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation [J]. Cell,1998,93(7):1231-40.
[110]ZANDI E, CHEN Y, KARIN M. Direct phosphorylation of IkappaB by IKKalpha and IKKbeta:discrimination between free and NF-kappaB-bound substrate [J]. Science,1998,281(5381): 1360-3.
[111]PAPATRIANTAFYLLOU M. Cell signalling:The NEMO guide to IkappaB [J]. Nature reviews Molecular cell biology,2012,13(7):408.
[112]WANG Y Y, RAN Y, SHU H B. Linear ubiquitination of NEMO brakes the antiviral response [J]. Cell host & microbe,2012,12(2):129-31.
[113]HEMMI H, TAKEUCHI O, SATO S, YAMAMOTO M, KAISHO T, SANJO H, KAWAI T, HOSHINO K, TAKEDA K, AKIRA S. The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection [J]. The Journal of experimental medicine,2004,199(12):1641-50.
[114]PERRY A K, CHOW E K, GOODNOUGH J B, YEH W C, CHENG G. Differential requirement for TANK-binding kinase-1 in type I interferon responses to toll-like receptor activation and viral infection [J]. The Journal of experimental medicine,2004,199(12):1651-8.
[115]TENOEVER B R, NG S L, CHUA M A, MCWHIRTER S M, GARCIA-SASTRE A, MANIATIS T. Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity [J]. Science,2007,315(5816):1274-8.
[116]CHOE J, KELKER M S, WILSON I A. Crystal structure of human toll-like receptor 3 (TLR3) ectodomain [J]. Science,2005,309(5734):581-5.
[117]WEN W, LIU W, YAN J, ZHANG M. Structure basis and unconventional lipid membrane binding properties of the PH-C1 tandem of rho kinases [J]. The Journal of biological chemistry,2008, 283(38):26263-73.
[118]ERMOLAEVA M A, MICHALLET M C, PAPADOPOULOU N, UTERMOHLEN O, KRANIDIOTI K, KOLLIAS G, TSCHOPP J, PASPARAKIS M. Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses [J]. Nature immunology,2008,9(9):1037-46.
[119]POBEZINSKAYA Y L, KIM Y S, CHOKSI S, MORGAN M J, LI T, LIU C, LIU Z. The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent Toll-like receptors [J]. Nature immunology,2008,9(9):1047-54.
[120]TAKEUCHI O, AKIRA S. Pattern recognition receptors and inflammation [J]. Cell,2010. 140(6):805-20.
[121]MANCUSO G, GAMBUZZA M, MIDIRI A, BIONDO C, PAPASERGI S, AKIRA S, TETI G, BENINATI C. Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells [J]. Nature immunology,2009,10(6):587-94.
[122]SANJUAN M A, MILASTA S, GREEN D R. Toll-like receptor signaling in the lysosomal pathways [J]. Immunological reviews,2009,227(1):203-20.
[123]HAAS T, METZGER J, SCHMITZ F, HEIT A. MULLER T, LATZ E, WAGNER H. The DNA sugar backbone 2' deoxyribose determines toll-like receptor 9 activation [J]. Immunity,2008, 28(3):315-23.
[124]HOSHINO K, SUGIYAMA T, MATSUMOTO M, TANAKA T, SAITO M, HEMMI H, OHARA O, AKIRA S, KAISHO T. IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9 [J]. Nature,2006,440(7086):949-53.
[125]UEMATSU S, SATO S, YAMAMOTO M, HIROTANI T, KATO H, TAKESHITA F, MATSUDA M, COBAN C. ISHII K J, KAWAI T, TAKEUCHI O, AKIRA S. Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7-and TLR9-mediated interferon-{alpha} induction [J]. The Journal of experimental medicine,2005,201(6):915-23.
[126]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. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6 [J]. Nature,2006, 439(7073):204-7.
[127]OGANESYAN G, SAHA S K, GUO B, HE J Q, SHAHANGIAN A, ZARNEGAR B, PERRY A, CHENG G. Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response [J]. Nature,2006,439(7073):208-11.
[128]SHINOHARA M L, LU L, BU J, WERNECK M B, KOBAYASHI K S, GLIMCHER L H, CANTOR H. Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells [J]. Nature immunology,2006,7(5):498-506.
[129]JOUNAI N, TAKESHITA F, KOBI YAM A K, S AWANO A, MIYAWAKI A, XIN K Q, ISHII K J, KAWAI T, AKIRA S, SUZUKI K, OKUDA K. The Atg5 Atg12 conjugate associates with innate antiviral immune responses [J]. Proceedings of the National Academy of Sciences of the United States of America,2007,104(35):14050-5.
[130]SAITO T, HIRAI R, LOO Y M, OWEN D, JOHNSON C L, SINHA S C, AKIRA S, FUJITA T, GALE M, JR. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2 [J]. Proceedings of the National Academy of Sciences of the United States of America,2007, 104(2):582-7.
[131]DIAO F, LI S, TIAN Y, ZHANG M, XU L G, ZHANG Y, WANG R P, CHEN D, ZHAI Z, ZHONG B, TIEN P, SHU H B. Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase [J]. Proceedings of the National Academy of Sciences of the United States of America,2007,104(28):11706-11.
[132]MOORE C B, BERGSTRALH D T, DUNCAN J A, LEI Y, MORRISON T E, ZIMMERMANN A G, ACCAVITTI-LOPER M A, MADDEN V J, SUN L, YE Z, LICH J D, HEISE M T, CHEN Z, TING J P. NLRX1 is a regulator of mitochondrial antiviral immunity [J]. Nature,2008, 451(7178):573-7.
[133]HUANG J, LIU T, XU L G, CHEN D, ZHAI Z, SHU H B. SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways [J]. The EMBO journal,2005,24(23):4018-28.
[134]YU Y, HAYWARD G S. The ubiquitin E3 ligase RAUL negatively regulates type i interferon through ubiquitination of the transcription factors IRF7 and IRF3 [J]. Immunity,2010,33(6):863-77.
[135]GACK M U, SHIN Y C, JOO C H, URANO T, LIANG C. SUN L, TAKEUCHI O, AKIRA S, CHEN Z, INOUE S,JUNG J U. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity [J]. Nature,2007,446(7138):916-20.
[136]VALLABHAPURAPU S, MATSUZAWA A, ZHANG W, TSENG P H, KEATS J J, WANG H, VIGNALI D A, BERGSAGEL P L, KARIN M. Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling [J]. Nature immunology,2008,9(12):1364-70.
[137]ZARNEGAR B J, WANG Y, MAHONEY D J, DEMPSEY P W, CHEUNG H H, HE J, SHIBA T, YANG X, YEH W C, MAK T W, KORNELUK R G, CHENG G. Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK [J]. Nature immunology,2008,9(12):1371-8.
[138]MAO A P, LI S, ZHONG B, LI Y, YAN J, LI Q, TENG C, SHU H B. Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for induction of interferon-beta (IFN-beta) and cellular antiviral response [J]. The Journal of biological chemistry,2010,285(13):9470-6.
[139]SPIES B, HOCHREIN H, VABULAS M, HUSTER K, BUSCH D H, SCHMITZ F, HEIT A, WAGNER H. Vaccination with plasmid DNA activates dendritic cells via Toll-like receptor 9 (TLR9) but functions in TLR9-deficient mice [J]. J Immunol,2003,171(11):5908-12.
[140]HEIT A, MAURER T, HOCHREIN H, BAUER S, HUSTER K M, BUSCH D H, WAGNER H. Cutting edge:Toll-like receptor 9 expression is not required for CpG DNA-aided cross-presentation of DNA-conjugated antigens but essential for cross-priming of CD8 T cells [J]. J Immunol,2003, 170(6):2802-5.
[141]STETSON D B, MEDZHITOV R. Recognition of cytosolic DNA activates an IRF3-dependent innate immune response [J]. Immunity,2006,24(1):93-103.
[142]SAITOH T, FUJITA N, YOSHIMORI T, AKIRA S. Regulation of dsDNA-induced innate immune responses by membrane trafficking [J]. Autophagy,2010,6(3):430-2.
[143]WANG Y Y, LIU L J, ZHONG B, LIU T T, LI Y, YANG Y, RAN Y, LI S, TIEN P, SHU H B. WDR5 is essential for assembly of the VISA-associated signaling complex and virus-triggered IRF3 and NF-kappaB activation [J]. Proceedings of the National Academy of Sciences of the United States of America,2010,107(2):815-20.
[144]LIU H M, LOO Y M, HORNER S M, ZORNETZER G A, KATZE M G, GALE M, JR. The mitochondrial targeting chaperone 14-3-3epsilon regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity [J]. Cell host & microbe,2012,11(5):528-37.
[145]RAMAGE R, GREEN J, MUIR T W, OGUNJOBI O M, LOVE S, SHAW K. Synthetic, structural and biological studies of the ubiquitin system:the total chemical synthesis of ubiquitin [J]. The Biochemical journal,1994,299 (Pt 1)(151-8.
[146]OGUNJOBI O, RAMAGE R. Ubiquitin:preparative chemical synthesis, purification and characterization [J]. Biochemical Society transactions,1990,18(6):1322-3.
[147]KERSCHER O, FELBERBAUM R, HOCHSTRASSER M. Modification of proteins by ubiquitin and ubiquitin-like proteins [J]. Annual review of cell and developmental biology,2006, 22(159-80.
[148]PICKART C M, FUSHMAN D. Polyubiquitin chains:polymeric protein signals [J]. Current opinion in chemical biology,2004,8(6):610-6.
[149]IKEDA F, DIKIC I. Atypical ubiquitin chains:new molecular signals.'Protein Modifications: Beyond the Usual Suspects' review series [J]. EMBO reports,2008,9(6):536-42.
[150]MATSUMOTO M L, WICKLIFFE K E, DONG K C, YU C, BOSANAC I, BUSTOS D, PHU L, KIRKPATRICK D S, HYMOWITZ S G, RAPE M, KELLEY R F, DIXIT V M. K11-linked polyubiquitination in cell cycle control revealed by a K11 linkage-specific antibody [J]. Molecular cell, 2010,39(3):477-84.
[151]IKEDA H, KERPPOLA T K. Lysosomal localization of ubiquitinated Jun requires multiple determinants in a lysine-27-linked polyubiquitin conjugate [J]. Molecular biology of the cell,2008, 19(11):4588-601.
[152]CHASTAGNER P, ISRAEL A, BROU C. AIP4/Itch regulates Notch receptor degradation in the absence of ligand [J]. PloS one,2008,3(7):e2735.
[153]MALYNN B A, MA A. Ubiquitin makes its mark on immune regulation [J]. Immunity,2010, 33(6):843-52.
[154]LIU S, CHEN Z J. Expanding role of ubiquitination in NF-kappaB signaling [J]. Cell research,2011,21(1):6-21.
[155]HERSHKO A, CIECHANOVER A. The ubiquitin system [J]. Annual review of biochemistry, 1998,67(425-79.
[156]MCGRATH J P, JENTSCH S, VARSHAVSKY A. UBA 1:an essential yeast gene encoding ubiquitin-activating enzyme [J]. The EMBO journal,1991,10(1):227-36.
[157]MICHALEK M T, GRANT E P, GRAMM C, GOLDBERG A L, ROCK K L. A role for the ubiquitin-dependent proteolytic pathway in MHC class I-restricted antigen presentation [J]. Nature, 1993,363(6429):552-4.
[158]PICKART C M. Mechanisms underlying ubiquitination [J]. Annual review of biochemistry, 2001,70(503-33.
[159]HOFMANN R M, PICKART C M. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair [J]. Cell,1999,96(5): 645-53.
[160]DENG L, WANG C, SPENCER E, YANG L, BRAUN A, YOU J, SLAUGHTER C, PICKART C, CHEN Z J. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain [J]. Cell,2000,103(2): 351-61.
[161]LIU Y C. Ubiquitin ligases and the immune response [J]. Annual review of immunology, 2004,22(81-127.
[162]HUIBREGTSE J M, SCHEFFNER M, BEAUDENON S, HOWLEY P M. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase [J]. Proceedings of the National Academy of Sciences of the United States of America,1995,92(7):2563-7.
[163]SCHEFFNER M, NUBER U, HUIBREGTSE J M. Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade [J]. Nature,1995,373(6509):81-3.
[164]FREEMONT P S. RING for destruction? [J]. Current biology:CB.2000,10(2):R84-7.
[165]JOAZEIRO C A, WEISSMAN A M. RING finger proteins:mediators of ubiquitin ligase activity [J]. Cell,2000,102(5):549-52.
[166]PERTEL T, HAUSMANN S, MORGER D, ZUGER S, GUERRA J, LASCANO J, REINHARD C, SANTONI F A, UCHIL P D, CHATEL L, BISIAUX A, ALBERT M L, STRAMBIO-DE-CASTILLIA C, MOTHES W, PIZZATO M, GRUTTER M G, LUBAN J. TRIM5 is an innate immune sensor for the retrovirus capsid lattice [J]. Nature,2011,472(7343):361-5.
[167]YANG K, SHI H X, LIU X Y, SHAN Y F, WEI B, CHEN S, WANG C. TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response [J]. J Immunol,2009,182(6): 3782-92.
[168]HIGGS R, NI GABHANN J, BEN LARBI N, BREEN E P, FITZGERALD K A, JEFFERIES C A. The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3 [J]. J Immunol,2008,181(3): 1780-6.
[169]HIGGS R, LAZZARI E, WYNNE C, NI GABHANN J, ESPINOSA A, WAHREN-HERLENIUS M, JEFFERIES C A. Self protection from anti-viral responses-Ro52 promotes degradation of the transcription factor IRF7 downstream of the viral Toll-Like receptors [J]. PloS one,2010,5(7):e11776.
[170]YOUNG J A, SERMWITTAYAWONG D, KIM H J, NANDU S, AN N, ERDJUMENT-BROMAGE H, TEMPST P, COSCOY L, WINOTO A. Fas-associated death domain (FADD) and the E3 ubiquitin-protein ligase TRIM21 interact to negatively regulate virus-induced interferon production [J]. The Journal of biological chemistry,2011,286(8):6521-31.
[171]ZHANG Z, BAO M, LU N, WENG L, YUAN B, LIU Y J. The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA [J]. Nature immunology,2013,14(2):172-8.
[172]ARIMOTO K, FUNAMI K, SAEKI Y, TANAKA K, OKAWA K, TAKEUCHI O, AKIRA S, MURAKAMI Y, SHIMOTOHNO K. Polyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense [J]. Proceedings of the National Academy of Sciences of the United States of America,2010,107(36):15856-61.
[173]POOLE E, GROVES I, MACDONALD A, PANG Y, ALCAMI A, SINCLAIR J. Identification of TRIM23 as a cofactor involved in the regulation of NF-kappaB by human cytomegalovirus [J]. Journal of virology,2009,83(8):3581-90.
[174]GACK M U, ALBRECHT R A, URANO T, INN K S, HUANG I C, CARNERO E, FARZAN M, INOUE S, JUNG J U, GARCIA-SASTRE A. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I [J]. Cell host & microbe,2009, 5(5):439-49.
[175]TSUCHIDA T, ZOU J, SAITOH T, KUMAR H, ABE T, MATSUURA Y, KAWAI T, AKIRA S. The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA [J]. Immunity,2010,33(5):765-76.
[176]OUYANG S, SONG X, WANG Y, RU H, SHAW N, JIANG Y, NIU F, ZHU Y, QIU W, PARVATIYAR K, LI Y, ZHANG R, CHENG G, LIU Z J. Structural analysis of the STING adaptor protein reveals a hydrophobic dimer interface and mode of cyclic di-GMP binding [J]. Immunity,2012, 36(6):1073-86.
[177]ZHAO W, WANG L, ZHANG M, YUAN C, GAO C. E3 ubiquitin ligase tripartite motif 38 negatively regulates TLR-mediated immune responses by proteasomal degradation of TNF receptor-associated factor 6 in macrophages [J]. J Immunol,2012,188(6):2567-74.
[178]ZHAO W, WANG L, ZHANG M, WANG P, YUAN C, QI J, MENG H, GAO C. Tripartite motif-containing protein 38 negatively regulates TLR3/4- and RIG-I-mediated IFN-beta production and antiviral response by targeting NAP1 [J]. J Immunol,2012,188(11):5311-8.
[179]XUE Q, ZHOU Z, LEI X, LIU X, HE B, WANG J, HUNG T. TRIM38 negatively regulates TLR3-MEdiated IFN-beta signaling by targeting TRIF for degradation [J]. PloS one,2012,7(10): e46825.
[180]ZHONG B, ZHANG L, LEI C, LI Y, MAO A P, YANG Y, WANG Y Y, ZHANG X L, SHU H B. The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA [J]. Immunity,2009,30(3):397-407.
[181]ZHONG B, ZHANG Y, TAN B, LIU T T, WANG Y Y, SHU H B. The E3 ubiquitin ligase RNF5 targets virus-induced signaling adaptor for ubiquitination and degradation [J]. J Immunol,2010, 184(11):6249-55.
[182]YOU F, SUN H, ZHOU X, SUN W, LIANG S, ZHAI Z, JIANG Z. PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4 [J]. Nature immunology,2009, 10(12):1300-8.
[183]ARIMOTO K, TAKAHASHI H, HISHIKI T, KONISHI H, FUJITA T, SHIMOTOHNO K. Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125 [J]. Proceedings of the National Academy of Sciences of the United States of America,2007,104(18):7500-5.
[184]GAO D, YANG Y K, WANG R P, ZHOU X, DIAO F C, LI M D, ZHAI Z H, JIANG Z F, CHEN D Y. REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-Ⅰ [J]. PloS one,2009,4(6):e5760.
[185]OSHIUMI H, MIYASHITA M, INOUE N, OKABE M, MATSUMOTO M, SEYA T. The ubiquitin ligase Riplet is essential for RIG-1-dependent innate immune responses to RNA virus infection [J]. Cell host & microbe,2010,8(6):496-509.
[186]NAKHAEI P, MESPLEDE T, SOLIS M, SUN Q, ZHAO T, YANG L, CHUANG T H, WARE C F, LIN R, HISCOTT J. The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS signaling pathway by targeting TRAF3 for degradation [J]. PLoS pathogens,2009,5(11): e1000650.
[187]CUI J, LI Y, ZHU L, LIU D, SONG YANG Z, WANG H Y, WANG R F. NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4 [J]. Nature immunology,2012,13(4):387-95.
[188]LI S, WANG L, BERMAN M, KONG Y Y, DORF M E. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production [J]. Immunity,2011,35(3): 426-40.
[189]ZHANG M, TIAN Y, WANG R P, GAO D, ZHANG Y, DIAO F C, CHEN D Y, ZHAI Z H, SHU H B. Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3 [J]. Cell research,2008,18(11):1096-104.
[190]MERONI G, DIEZ-ROUX G. TRIM/RBCC, a novel class of'single protein RING finger' E3 ubiquitin ligases [J]. BioEssays:news and reviews in molecular, cellular and developmental biology, 2005,27(11):1147-57.
[191]OZATO K, SHIN D M, CHANG T H, MORSE H C,3RD. TRIM family proteins and their emerging roles in innate immunity [J]. Nature reviews Immunology,2008,8(11):849-60.
[192]SARDIELLO M, CAIRO S, FONTANELLA B, BALLABIO A, MERONI G. Genomic analysis of the TRIM family reveals two groups of genes with distinct evolutionary properties [J]. BMC evolutionary biology,2008,8(225.
[193]SHORT K M, COX T C. Subclassification of the RBCC/TRIM superfamily reveals a novel motif necessary for microtubule binding [J]. The Journal of biological chemistry,2006,281(13): 8970-80.
[194]VERSTEEG G A, RAJSBAUM R, SANCHEZ-APARICIO M T, MAESTRE A M. VALDIVIEZO J, SHI M, INN K S, FERNANDEZ-SESMA A, JUNG J, GARCTA-SASTRE A. The E3-Ligase TRIM Family of Proteins Regulates Signaling Pathways Triggered by Innate Immune Pattern-Recognition Receptors [J]. Immunity,2013,38(2):384-98.
[195]KAWAI T, AKIRA S. Regulation of innate immune signalling pathways by the tripartite motif (TRIM) family proteins [J]. EMBO molecular medicine,2011,3(9):513-27.
[196]SHEN Y, LI N L, WANG J, LIU B, LESTER S, LI K. TRIM56 is an essential component of the TLR3 antiviral signaling pathway [J]. The Journal of biological chemistry,2012,287(43): 36404-13.
[197]LIANG Q, DENG H, LI X, WU X, TANG Q, CHANG T H, PENG H, RAUSCHER F J, 3RD, OZATO K, ZHU F. Tripartite motif-containing protein 28 is a small ubiquitin-related modifier E3 ligase and negative regulator of IFN regulatory factor 7 [J]. J Immunol,2011,187(9):4754-63.
[198]ZHA J, HAN K J, XU L G, HE W, ZHOU Q, CHEN D, ZHAI Z, SHU H B. The Ret finger protein inhibits signaling mediated by the noncanonical and canonical IkappaB kinase family members [J]. J Immunol,2006,176(2):1072-80.
[199]SHI M, DENG W, BI E, MAO K, JI Y, LIN G, WU X, TAO Z, LI Z, CAI X, SUN S, XIANG C, SUN B. TRIM30 alpha negatively regulates TLR-mediated NF-kappa B activation by targeting TAB2 and TAB3 for degradation [J]. Nature immunology,2008,9(4):369-77.
[200]LOCKE M, TINSLEY C L, BENSON M A, BLAKE D J. TRIM32 is an E3 ubiquitin ligase for dysbindin [J]. Human molecular genetics,2009,18(13):2344-58.
[201]KUDRYASHOVA E, KUDRYASHOV D, KRAMEROVA I, SPENCER M J. Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2H that binds to skeletal muscle myosin and ubiquitinates actin [J]. Journal of molecular biology,2005,354(2):413-24.
[202]ALBOR A, EL-HIZAWI S, HORN E J, LAEDERICH M, FROSK P, WROGEMANN K, KULESZ-MARTIN M. The interaction of Piasy with Trim32, an E3-ubiquitin ligase mutated in limb-girdle muscular dystrophy type 2H, promotes Piasy degradation and regulates UVB-induced keratinocyte apoptosis through NFkappaB [J]. The Journal of biological chemistry,2006,281(35): 25850-66.
[203]KANO S, MIYAJIMA N, FUKUDA S, HATAKEYAMA S. Tripartite motif protein 32 facilitates cell growth and migration via degradation of Abl-interactor 2 [J]. Cancer research,2008, 68(14):5572-80.
[204]SCHWAMBORN J C, BEREZIKOV E, KNOBLICH J A. The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors [J]. Cell,2009,136(5): 913-25.
[205]KUDRYASHOVA E, STRUYK A, MOKHONOVA E, CANNON S C, SPENCER M J. The common missense mutation D489N in TRIM32 causing limb girdle muscular dystrophy 2H leads to loss of the mutated protein in knock-in mice resulting in a Trim32-null phenotype [J]. Human molecular genetics,2011,20(20):3925-32.
[206]HORN E J, ALBOR A, LIU Y, EL-HIZAWI S, VANDERBEEK G E, BABCOCK M, BOWDEN G T, HENNINGS H, LOZANO G, WEINBERG W C, KULESZ-MARTIN M. RING protein Trim32 associated with skin carcinogenesis has anti-apoptotic and E3-ubiquitin ligase properties [J]. Carcinogenesis,2004,25(2):157-67.
[207]LIU Y, LAGOWSKI J P, GAO S, RAYMOND J H, WHITE C R, KULESZ-MARTIN M F. Regulation of the psoriatic chemokine CCL20 by E3 ligases Trim32 and Piasy in keratinocytes [J]. The Journal of investigative dermatology,2010,130(5):1384-90.
[208]KUDRYASHOVA E, WU J, HAVTON L A, SPENCER M J. Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component [J]. Human molecular genetics,2009,18(7):1353-67.
[209]NICKLAS S, OTTO A, WU X, MILLER P, STELZER S, WEN Y, KUANG S, WROGEMANN K, PATEL K, DING H, SCHWAMBORN J C. TRIM32 regulates skeletal muscle stem cell differentiation and is necessary for normal adult muscle regeneration [J]. PloS one,2012,7(1): e30445.