Ubiquitination in the antiviral immune response

Virology

Volumn 479-480, Issue , 2015, Pages 52-65

  Davis, Meredith E ^a   Gack, Michaela U ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Antiviral immunity; CGAS; E3 ligases; RIG I like receptors; STING; Toll like receptors; TRIM proteins; TRIM25; Type I interferon; Ubiquitin

Indexed keywords

CYTOKINE; DEAD BOX PROTEIN; NUCLEOTIDYLTRANSFERASE; TOLL LIKE RECEPTOR;

HOST PATHOGEN INTERACTION; IMMUNOLOGY; INNATE IMMUNITY; METABOLISM; SECRETION (PROCESS); SIGNAL TRANSDUCTION; UBIQUITINATION; VIRUS;

CYTOKINES; DEAD-BOX RNA HELICASES; HOST-PATHOGEN INTERACTIONS; IMMUNITY, INNATE; NUCLEOTIDYLTRANSFERASES; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS; UBIQUITINATION; VIRUSES;

EID: 84937511251     PISSN: 00426822     EISSN: 10960341     Source Type: Journal    
DOI: 10.1016/j.virol.2015.02.033     Document Type: Review

References (185)

1. Ablasser A., et al. cGAS produces a 2[prime]-5[prime]-linked cyclic dinucleotide second messenger that activates STING. Nature 2013, 498(7454):380-384.
2. Akira S., Takeda K. Toll-like receptor signalling. Nat. Rev. Immunol. 2004, 4(7):499-511.
3. Al-Hakim A.K., et al. Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains. Biochem. J. 2008, 411(2):249-260.
4. Andrejeva J., et al. The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc. Natl. Acad. Sci. USA 2004, 101(49):17264-17269.
5. Arimoto K.-i., et al. Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proc. Natl. Acad. Sci. USA 2007, 104(18):7500-7505.
6. Arimoto K.-i., et al. Polyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense. Proc. Natl. Acad. Sci. USA 2010, 107(36):15856-15861.
7. Ashida H., et al. A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response. Nat. Cell Biol. 2010, 12(1):66-73. Supp. 1-9.
8. Belgnaoui S., et al. Linear ubiquitination of NEMO negatively regulates the interferon antiviral response through disruption of the MAVS-TRAF3 complex. Cell Host Microbe 2012, 12(2):211-222.
9. Belgnaoui S.M., Paz S., Hiscott J. Orchestrating the interferon antiviral response through the mitochondrial antiviral signaling (MAVS) adapter. Curr. Opin. Immunol. 2011, 23(5):564-572.
10. Berndsen C.E., Wolberger C. New insights into ubiquitin E3 ligase mechanism. Nat. Struct. Mol. Biol. 2014, 21(4):301-307.
11. Bhoj V.G., Chen Z.J. Ubiquitylation in innate and adaptive immunity. Nature 2009, 458(7237):430-437.
12. Boname J.M., et al. Efficient internalization of MHC I requires lysine-11 and lysine-63 mixed linkage polyubiquitin chains. Traffic 2010, 11(2):210-220.
13. Boone D.L., et al. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat. Immunol. 2004, 5(10):1052-1060.
14. Brunette R.L., et al. Extensive evolutionary and functional diversity among mammalian AIM2-like receptors. J. Exp. Med. 2012, 209(11):1969-1983.
15. Burdette D.L., et al. STING is a direct innate immune sensor of cyclic di-GMP. Nature 2011, 478(7370):515-518.
16. Chang M., Jin W., Sun S.C. Peli1 facilitates TRIF-dependent Toll-like receptor signaling and proinflammatory cytokine production. Nat. Immunol. 2009, 10(10):1089-1095.
17. Chen J., Chen Z.J. Regulation of NF-kappaB by ubiquitination. Curr. Opin. Immunol. 2013, 25(1):4-12.
18. Chernorudskiy A.L., Gainullin M.R. Ubiquitin system: direct effects join the signaling. Sci. Signal. 2013, 6:pe22.
19. Chiang J.J., Davis M.E., Gack M.U. Regulation of RIG-I-like receptor signaling by host and viral proteins. Cytokine Growth Factor Rev 2014, 25(5):491-505.
20. Chuang T.H., Ulevitch R.J. Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors. Nat. Immunol. 2004, 5(5):495-502.
21. Colleran A., et al. Deubiquitination of NF-kappaB by ubiquitin-specific protease-7 promotes transcription. Proc. Natl. Acad. Sci. USA 2013, 110(2):618-623.
22. Conze D.B., et al. Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation. Mol. Cell. Biol. 2008, 28(10):3538-3547.
23. Creagh E.O.N. LA TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity. Trends Immunol. 2006, 27:352-357.
24. Cui J., et al. NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4. Nat. Immunol. 2012, 13(4):387-395.
25. Cui J., et al. USP3 inhibits type I interferon signaling by deubiquitinating RIG-I-like receptors. Cell Res. 2014, 24(4):400-416.
26. Deng L., et al. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 2000, 103(2):351-361.
27. Diner E.J., et al. The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell Rep. 2013, 3(5):1355-1361.
28. Dynek J.N., et al. c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J. 2010, 29:4198-4209.
29. Ea C.K., et al. Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol. Cell 2006, 22(2):245-257.
30. Fan Y., et al. USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase. J. Exp. Med. 2014, 211(2):313-328.
31. Fearns C., et al. Triad3A regulates ubiquitination and proteasomal degradation of RIP1 following disruption of Hsp90 binding. J. Biol. Chem. 2006, 281(45):34592-34600.
32. Friedman C.S., et al. The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. EMBO Rep. 2008, 9:930-936.
33. Gack M. TRIMming Flavivirus infection. Cell Host Microbe 2011, 10(3):175-177.
34. Gack M., et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 2007, 446(7138):916-920.
35. Gack M., et al. Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction. Proc. Natl. Acad. Sci. USA 2008, 105(43):16743-16748.
36. Gack M., et al. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe 2009, 5(5):439-449.
37. Gack M.U. Mechanisms of RIG-I-Like receptor activation and manipulation by viral pathogens. J. Virol. 2014, 88(10):5213-5216.
38. Gack M.U., et al. Phosphorylation-mediated negative regulation of RIG-I antiviral activity. J. Virol. 2010, 84(7):3220-3229.
39. Gao D., et al. REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I. PloS one 2009, 4(6):e5760.
40. Gay N.J., et al. Assembly and localization of Toll-like receptor signalling complexes. Nat. Rev. Immunol. 2014, 14(8):546-558.
41. Geisler S., et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat. Cell Biol. 2010, 12(2):119-131.
42. Geng H., et al. Phosphorylation of NF-kappaB p65 at Ser468 controls its COMMD1-dependent ubiquitination and target gene-specific proteasomal elimination. EMBO Rep. 2009, 10(4):381-386.
43. Gerlach B., et al. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature 2011, 471(7340):591-596.
44. Glauser L., et al. Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor mitofusin 1. J. Neurochem. 2011, 118(4):636-645.
45. Goto E., et al. Contribution of lysine 11-linked ubiquitination to MIR2-mediated major histocompatibility complex class I internalization. J. Biol. Chem. 2010, 285(46):35311-35319.
46. Goubau D., Deddouche S., Reis e Sousa C. Cytosolic sensing of viruses. Immunity 2013, 38(5):855-869.
47. Goubau D., et al. Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates. Nature 2014, 514(7522):372-375.
48. Hayden M.S., Ghosh S. Shared principles in NF-kappaB signaling. Cell 2008, 132(3):344-362.
49. Heissmeyer V., et al. Shared pathways of IkappaB kinase-induced SCF(betaTrCP)-mediated ubiquitination and degradation for the NF-kappaB precursor p105 and IkappaBalpha. Mol. Cell. Biol. 2001, 21(4):1024-1035.
50. Henderson G., Zhang Y., Jones C. The Bovine herpesvirus 1 gene encoding infected cell protein 0 (bICP0) can inhibit interferon-dependent transcription in the absence of other viral genes. J. Gen. Virol. 2005, 86(Pt 10):2697-2702.
51. Higgs R., et al. The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3. J. Immunol. 2008, 181(3):1780-1786.
52. Hu H., et al. OTUD7B controls non-canonical NF-kappaB activation through deubiquitination of TRAF3. Nature 2013, 494(7437):371-374.
53. Huang H., et al. K33-linked polyubiquitination of T cell receptor-ζ regulates proteolysis-independent T cell signaling. Immunity 2010, 33(1):60-70.
54. Ikeda F., Crosetto N., Dikic I. What determines the specificity and outcomes of ubiquitin signaling?. Cell 2010, 143(5):677-681.
55. Ikeda F., et al. SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB activity and apoptosis. Nature 2011, 471(7340):637-641.
56. Inn K.-S., et al. Linear ubiquitin assembly complex negatively regulates RIG-I- and TRIM25-mediated type I interferon induction. Mol. Cell 2011, 41(3):354-365.
57. Ishikawa H., Barber G. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 2008, 455(7213):674-678.
58. Ishikawa H., Ma Z., Barber G.N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 2009, 461(7265):788-792.
59. Ivashkiv L.B., Donlin L.T. Regulation of type I interferon responses. Nat. Rev. Immunol. 2014, 14(1):36-49.
60. Ivins F.J., et al. NEMO oligomerization and its ubiquitin-binding properties. Biochem. J. 2009, 421(2):243-251.
61. Jensen L.E., Whitehead A.S. Ubiquitin activated tumor necrosis factor receptor associated factor-6 (TRAF6) is recycled via deubiquitination. FEBS Lett. 2003, 553(1-2):190-194.
62. Jiang X., et al. Ubiquitin-induced oligomerization of the RNA sensors RIG-I and MDA5 activates antiviral innate immune response. Immunity 2012, 36(6):959-973.
63. Jiang Z., et al. Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex. J. Biol. Chem. 2003, 278(13):10952-10956.
64. Karim R., et al. Human papillomavirus (HPV) upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte[U+05F3]s innate immune response. PLoS Pathog. 2013, 9(5):e1003384.
65. Kato H., Fujita T. Autoimmunity caused by constitutive activation of cytoplasmic viral RNA sensors. Cytokine Growth Factor Rev 2014, 25(6):739-743.
66. Kato H., et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006, 441(7089):101-105.
67. Kawai T., et al. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat. Immunol. 2005, 6(10):981-988.
68. Kayagaki N., et al. DUBA: a deubiquitinase that regulates type I interferon production. Science 2007, 318(5856):1628-1632.
69. Kim W., et al. Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol. Cell 2011, 44(2):325-340.
70. Kirisako T., et al. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J. 2006, 25(20):4877-4887.
71. Kirkpatrick D.S., et al. Quantitative analysis of in vitro ubiquitinated cyclin B1 reveals complex chain topology. Nat. Cell Biol. 2006, 8(7):700-710.
72. Koegl M., et al. A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. Cell 1999, 96(5):635-644.
73. Kranzusch P.J., et al. Structure of human cGAS reveals a conserved family of second-messenger enzymes in innate immunity. Cell Rep. 2013, 3(5):1362-1368.
74. Kravtsova-Ivantsiv Y., Ciechanover A. Non-canonical ubiquitin-based signals for proteasomal degradation. J. Cell. Sci. 2012, 125(Pt 3):539-548.
75. Kulathu Y., Komander D. Atypical ubiquitylation - the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages. Nat. Rev. Mol. Cell Biol. 2012, 13(8):508-523.
76. Kuniyoshi K., et al. Pivotal role of RNA-binding E3 ubiquitin ligase MEX3C in RIG-I-mediated antiviral innate immunity. Proc. Natl. Acad. Sci. USA 2014, 111(15):5646-5651.
77. Lee Y.S., et al. Smad6-specific recruitment of Smurf E3 ligases mediates TGF-beta1-induced degradation of MyD88 in TLR4 signalling. Nat. Commun. 2011, 2:460.
78. Li S., et al. Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6. J. Biol. Chem. 2010, 285(7):4291-4297.
79. Li S., et al. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. Immunity 2011, 35(3):426-440.
80. Li X.-D., et al. Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects. Science (New York, N.Y.) 2013, 341(6152):1390-1394.
81. Lin R., et al. Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation. Mol. Cell. Biol. 1998, 18(5):2986-2996.
82. Lin R., et al. The herpes simplex virus ICP0 RING finger domain inhibits IRF3- and IRF7-mediated activation of interferon-stimulated genes. J. Virol. 2004, 78(4):1675-1684.
83. Liu S.Y., Sanchez D.J., Cheng G. New developments in the induction and antiviral effectors of type I interferon. Curr. Opin. Immunol. 2011, 23(1):57-64.
84. Lo Y.C., et al. Structural basis for recognition of diubiquitins by NEMO. Mol. Cell 2009, 33(5):602-615.
85. Loo Y.-M., Gale M. Immune signaling by RIG-I-like receptors. Immunity 2011, 34(5):680-692.
86. Maharaj N.P., et al. Conventional protein kinase C-alpha (PKC-alpha) and PKC-beta negatively regulate RIG-I antiviral signal transduction. J. Virol. 2012, 86(3):1358-1371.
87. Maine G.N., et al. COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase. EMBO J. 2007, 26(2):436-447.
88. Maniatis T. A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and Hedgehog signaling pathways. Genes Dev. 1999, 13(5):505-510.
89. Matsumoto M.L., et al. K11-linked polyubiquitination in cell cycle control revealed by a K11 linkage-specific antibody. Mol. Cell 2010, 39(3):477-484.
90. Mattiroli F., Sixma T.K. Lysine-targeting specificity in ubiquitin and ubiquitin-like modification pathways. Nat. Struct. Mol. Biol. 2014, 21(4):308-316.
91. McDowell G.S., Philpott A. Non-canonical ubiquitylation: mechanisms and consequences. Int. J. Biochem. Cell Biol. 2013, 45(8):1833-1842.
92. McNab F., et al. Tripartite-motif proteins and innate immune regulation. Curr. Opin. Immunol. 2011, 23(1):46-56.
93. Medzhitov R. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 2001, 1(2):135-145.
94. Meylan E., et al. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 2005, 437(7062):1167-1172.
95. Nagy V., Dikic I. Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity. Biol. Chem. 2010, 391(2-3):163-169.
96. Naiki Y., et al. Transforming growth factor-beta differentially inhibits MyD88-dependent, but not TRAM- and TRIF-dependent, lipopolysaccharide-induced TLR4 signaling. J. Biol. Chem. 2005, 280(7):5491-5495.
97. Nakasone M.A., et al. Mixed-linkage ubiquitin chains send mixed messages. Structure 2013, 21(5):727-740.
98. Nakhaei P., et al. The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS signaling pathway by targeting TRAF3 for degradation. PLoS Pathog. 2009, 5(11):e1000650.
99. Narayan K., et al. TRIM13 is a negative regulator of MDA5-mediated type I IFN production. J. Virol. 2014, 88(18):10748-10757.
100. Nistal-Villan E., et al. Negative role of RIG-I serine 8 phosphorylation in the regulation of interferon-beta production. J. Biol. Chem. 2010, 285(26):20252-20261.
101. O'Neill L.A., Bowie A.G. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol. 2007, 7(5):353-364.
102. Oganesyan G., et al. Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 2006, 439(7073):208-211.
103. Ordureau A., et al. The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1. Biochem. J. 2008, 409(1):43-52.
104. Oshiumi H., et al. Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote interferon-beta induction during the early phase of viral infection. J. Biol. Chem. 2009, 284(2):807-817.
105. Oshiumi H., et al. The ubiquitin ligase Riplet is essential for RIG-I-dependent innate immune responses to RNA virus infection. Cell Host Microbe 2010, 8(6):496-509.
106. Oshiumi H., et al. A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses. PLoS Pathog 2013, 9(8):e1003533.
107. Pan Y., et al. Smurf2 negatively modulates RIG-I-dependent antiviral response by targeting VISA/MAVS for ubiquitination and degradation. J. Immunol. 2014, 192(10):4758-4764.
108. Parvatiyar K., Barber G.N., Harhaj E.W. TAX1BP1 and A20 inhibit antiviral signaling by targeting TBK1-IKKi kinases. J. Biol. Chem. 2010, 285(20):14999-15009.
109. Pauli, E.-K., et al., The ubiquitin-specific protease USP15 promotes RIG-I-mediated antiviral signaling by deubiquitylating TRIM25, Sci. Signal.. 7. 2014. ra3.
110. Paz S., et al. Ubiquitin-regulated recruitment of IkappaB kinase epsilon to the MAVS interferon signaling adapter. Mol. Cell Biol. 2009, 29(12):3401-3412.
111. Paz S., et al. A functional C-terminal TRAF3-binding site in MAVS participates in positive and negative regulation of the IFN antiviral response. Cell Res. 2011, 21(6):895-910.
112. Peisley A., et al. Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I. Nature 2014, 509(7498):110-114.
113. Peng D.-J., et al. Noncanonical K27-linked polyubiquitination of TIEG1 regulates Foxp3 expression and tumor growth. J. Immunol. 2011, 186(10):5638-5647.
114. Peng Y., Xu R., Zheng X. HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1. PLoS Pathog. 2014, 10(4):e1004041.
115. Pickart C.M., Eddins M.J. Ubiquitin: structures, functions, mechanisms. Biochim. Biophys. Acta 2004, 1695(1-3):55-72.
116. Qin Y., et al. RNF26 temporally regulates virus-triggered Type I interferon induction by two distinct mechanisms. PLoS Pathog. 2014, 10(9):e1004358.
117. Rahighi S., et al. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Cell 2009, 136(6):1098-1109.
118. Rajsbaum R., et al. Species-specific inhibition of RIG-I ubiquitination and IFN induction by the influenza A virus NS1 protein. PLoS Pathog. 2012, 8(11):e1003059.
119. Rajsbaum R., et al. Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKepsilon kinase-mediated antiviral response. Immunity 2014, 40(6):880-895.
120. Rajsbaum R., Garcia-Sastre A., Versteeg G.A. TRIMmunity: the roles of the TRIM E3-ubiquitin ligase family in innate antiviral immunity. J. Mol. Biol. 2014, 426(6):1265-1284.
121. Reyes-Turcu F.E., Ventii K.H., Wilkinson K.D. Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu. Rev. Biochem. 2009, 78(1):363-397.
122. Rodriguez K.R., Bruns A.M., Horvath C.M. MDA5 and LGP2: accomplices and antagonists of antiviral signal transduction. J Virol 2014, 88(15):8194-8200.
123. Saccani S., et al. Degradation of promoter-bound p65/RelA is essential for the prompt termination of the nuclear factor kappaB response. J. Exp. Med. 2004, 200(1):107-113.
124. Sadler A.J., Williams B.R. Interferon-inducible antiviral effectors. Nat. Rev Immunol. 2008, 8(7):559-568.
125. Saha S., et al. Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif. EMBO J. 2006, 25(14):3257-3263.
126. Saira K., Zhou Y., Jones C. The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) induces degradation of interferon response factor 3 and, consequently, inhibits beta interferon promoter activity. J. Virol. 2007, 81(7):3077-3086.
127. Saitoh T., et al. Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1. Nat. Immunol. 2006, 7(6):598-605.
128. Sauer J.D., et al. The N-ethyl-N-nitrosourea-induced Goldenticket mouse mutant reveals an essential function of Sting in the in vivo interferon response to Listeria monocytogenes and cyclic dinucleotides. Infect. Immun. 2011, 79(2):688-694.
129. Schauvliege R., Janssens S., Beyaert R. Pellino proteins are more than scaffold proteins in TLR/IL-1R signalling: a role as novel RING E3-ubiquitin-ligases. FEBS Lett. 2006, 580(19):4697-4702.
130. Schauvliege R., Janssens S., Beyaert R. Pellino proteins: novel players in TLR and IL-1R signalling. J. Cell. Mol. Med. 2007, 11(3):453-461.
131. Schlee M. Master sensors of pathogenic RNA - RIG-I like receptors. Immunobiology 2013, 218(11):1322-1335.
132. Sen G.C., Sarkar S.N. The interferon-stimulated genes: targets of direct signaling by interferons, double-stranded RNA, and viruses. Curr. Top. Microbiol. Immunol. 2007, 316:233-250.
133. Seth R.B., et al. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 2005, 122(5):669-682.
134. Shembade N., Ma A., Harhaj E.W. Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes. Science 2010, 327(5969):1135-1139.
135. Smith S., Jefferies C. Role of DNA/RNA sensors and contribution to autoimmunity. Cytokine Growth Factor Rev. 2014, 25(6):745-757.
136. Spratt D.E., Walden H., Shaw G.S. RBR E3 ubiquitin ligases: new structures, new insights, new questions. Biochem. J. 2014, 458(3):421-437.
137. Sun L., et al. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 2013, 339(6121):786-791.
138. Takaoka A., et al. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 2007, 448(7152):501-505.
139. Takeuchi O., Akira S. Pattern recognition receptors and inflammation. Cell 2010, 140(6):805-820.
140. Tanaka T., Grusby M.J., Kaisho T. PDLIM2-mediated termination of transcription factor NF-kappaB activation by intranuclear sequestration and degradation of the p65 subunit. Nat. Immunol. 2007, 8(6):584-591.
141. Thoms H.C., et al. Nucleolar targeting of RelA(p65) is regulated by COMMD1-dependent ubiquitination. Cancer Res. 2010, 70(1):139-149.
142. Tokunaga F., et al. Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation. Nat. Cell Biol. 2009, 11(2):123-132.
143. Tokunaga F., et al. SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain assembly complex. Nature 2011, 471(7340):633-636.
144. Tsuchida T., et al. The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA. Immunity 2010, 33(5):765-776.
145. Tu D., et al. Structure and ubiquitination-dependent activation of TANK-binding kinase 1. Cell Rep. 2013, 3(3):747-758.
146. Unterholzner L., et al. IFI16 is an innate immune sensor for intracellular DNA. Nat. Immunol. 2010, 11(11):997-1004.
147. Wagner S.A., et al. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Mol. Cell Proteomics 2011, 10(10):M111. 013284.
148. Walczak H., Iwai K., Dikic I. Generation and physiological roles of linear ubiquitin chains. BMC Biol. 2012, 10:23.
149. Wang C., et al. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 2001, 412(6844):346-351.
150. Wang C., et al. The E3 ubiquitin ligase Nrdp1 [U+05F3]preferentially[U+05F3] promotes TLR-mediated production of type I interferon. Nat. Immunol. 2009, 10(7):744-752.
151. Wang L., Li S., Dorf M.E. NEMO binds ubiquitinated TANK-binding kinase 1 (TBK1) to regulate innate immune responses to RNA viruses. PLoS One 2012, 7(9):e43756.
152. Wang L., et al. USP4 positively regulates RIG-I-mediated antiviral response through deubiquitination and stabilization of RIG-I. J. Virol. 2013, 87(8):4507-4515.
153. Wang Y., Tong X., Ye X. Ndfip1 Negatively Regulates RIG-I-dependent immune signaling by enhancing E3 ligase Smurf1-mediated MAVS degradation. J. Immunol. 2012, 189(11):5304-5313.
154. Wang Y.Y., et al. A20 is a potent inhibitor of TLR3- and Sendai virus-induced activation of NF-kappaB and ISRE and IFN-beta promoter. FEBS Lett. 2004, 576(1-2):86-90.
155. Wenzel D.M., et al. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 2011, 474(7349):105-108.
156. Wertz I.E., et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 2004, 430(7000):694-699.
157. Wies E., et al. Dephosphorylation of the RNA sensors RIG-I and MDA5 by the phosphatase PP1 is essential for innate immune signaling. Immunity 2013, 38(3):437-449.
158. Wu B., et al. Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5. Cell 2013, 152(1-2):276-289.
159. Wu J., et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 2013, 339(6121):826-830.
160. Xia Z.P., et al. Direct activation of protein kinases by unanchored polyubiquitin chains. Nature 2009, 461(7260):114-119.
161. Xu L.G., et al. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol. Cell 2005, 19(6):727-740.
162. Yan J., et al. TRIM4 modulates type I interferon induction and cellular antiviral response by targeting RIG-I for K63-linked ubiquitination. J. Mol. Cell Biol. 2014, 6(2):154-163.
163. Yang B., et al. Novel function of Trim44 promotes an antiviral response by stabilizing VISA. J. Immunol. 2013, 190(7):3613-3619.
164. Yang Y., et al. E3 ligase WWP2 negatively regulates TLR3-mediated innate immune response by targeting TRIF for ubiquitination and degradation. Proc. Natl. Acad. Sci. USA 2013, 110(13):5115-5120.
165. Yaron A., et al. Identification of the receptor component of the I[kappa]B[alpha]-ubiquitin ligase. Nature 1998, 396(6711):590-594.
166. Ye J.S., et al. Lysine 63-linked TANK-binding kinase 1 ubiquitination by mindbomb E3 ubiquitin protein ligase 2 is mediated by the mitochondrial antiviral signaling protein. J. Virol. 2014, 88(21):12765-12776.
167. Yoneyama M., et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 2004, 5(7):730-737.
168. You F., et al. PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4. Nat. Immunol. 2009, 10(12):1300-1308.
169. Young J.A., et al. Fas-associated death domain (FADD) and the E3 ubiquitin-protein ligase TRIM21 interact to negatively regulate virus-induced interferon production. J. Biol. Chem. 2011, 286(8):6521-6531.
170. Yu Y., Hayward G.S. The ubiquitin E3 ligase RAUL negatively regulates type i interferon through ubiquitination of the transcription factors IRF7 and IRF3. Immunity 2010, 33(6):863-877.
171. Zeng W., et al. Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3. Mol. Cell 2009, 36(2):315-325.
172. Zeng W., et al. Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell 2010, 141(2):315-330.
173. Zhang J., et al. Impaired regulation of NF-kappaB and increased susceptibility to colitis-associated tumorigenesis in CYLD-deficient mice. J. Clin. Invest. 2006, 116(11):3042-3049.
174. Zhang J., et al. TRIM32 protein modulates type I interferon induction and cellular antiviral response by targeting MITA/STING protein for K63-linked ubiquitination. J. Biol. Chem. 2012, 287(34):28646-28655.
175. Zhang L., et al. Ubiquitin-specific protease 2b negatively regulates IFN-beta production and antiviral activity by targeting TANK-binding kinase 1. J. Immunol. 2014, 193(5):2230-2237.
176. Zhang M., et al. Regulation of IkappaB kinase-related kinases and antiviral responses by tumor suppressor CYLD. J. Biol. Chem. 2008, 283(27):18621-18626.
177. Zhang M., et al. Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3. Cell Res. 2008, 18(11):1096-1104.
178. Zhang M., et al. TRAF-interacting protein (TRIP) negatively regulates IFN-beta production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1. J. Exp. Med. 2012, 209(10):1703-1711.
179. Zhang X., et al. The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop. Cell Rep. 2014, 6(3):421-430.
180. Zhang Z., et al. The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nat. Immunol. 2011, 12(10):959-965.
181. Zhao W., et al. E3 ubiquitin ligase tripartite motif 38 negatively regulates TLR-mediated immune responses by proteasomal degradation of TNF receptor-associated factor 6 in macrophages. J. Immunol. 2012, 188(6):2567-2574.
182. Zhong B., et al. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 2008, 29(4):538-550.
183. Zhong B., et al. The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA. Immunity 2009, 30(3):397-407.
184. Zhong B., et al. The E3 ubiquitin ligase RNF5 targets virus-induced signaling adaptor for ubiquitination and degradation. J. Immunol. 2010, 184(11):6249-6255.
185. Zotti T., et al. TRAF7 protein promotes Lys-29-linked polyubiquitination of IkappaB kinase (IKKgamma)/NF-kappaB essential modulator (NEMO) and p65/RelA protein and represses NF-kappaB activation. J. Biol. Chem. 2011, 286(26):22924-22933.