Mitochondrial antiviral-signaling protein (MAVS) is a protein that in humans is encoded by the MAVSgene.[1][2][3] The protein is also known by the names VISA (virus-induced signaling adapter), IPS-1 and Cardif. Aggregated MAVS forms protease resistant prion-like aggregates that activate IRF3 dimerization.[4]
Function
Double-stranded RNA viruses are recognized in a cell type-dependent manner by the transmembrane receptor TLR3 or by the cytoplasmic RNA helicases MDA5 and RIGI. These interactions initiate signaling pathways that differ in their initial steps but converge in the activation of the protein kinases IKKA (CHUK) and IKKB (IKBKB; MIM 603258), which activate NFKB, or TBK1 and IKBKE (IKBKE), which activate IRF3. Activated IRF3 and NFKB induce transcription of IFNβ (IFNB1). For the TLR3 pathway, the intermediary molecule before the pathways converge is the cytoplasmic protein TRIF (TICAM1). For RIGI, the intermediary protein is mitochondria-bound MAVS.[3][5]
References
↑Seth RB, Sun L, Ea CK, Chen ZJ (Sep 2005). "Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3". Cell. 122 (5): 669–82. doi:10.1016/j.cell.2005.08.012. PMID16125763.
↑Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB (Sep 2005). "VISA is an adapter protein required for virus-triggered IFN-beta signaling". Mol Cell. 19 (6): 727–40. doi:10.1016/j.molcel.2005.08.014. PMID16153868.
Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O (2000). "Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (5): 337–45. doi:10.1093/dnares/6.5.337. PMID10574462.
Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S (2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways". Oncogene. 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID12761501.
Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S (2005). "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction". Nat. Immunol. 6 (10): 981–8. doi:10.1038/ni1243. PMID16127453.
Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J (2005). "Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus". Nature. 437 (7062): 1167–72. doi:10.1038/nature04193. PMID16177806.
Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS (2006). "Transcriptome analysis of human gastric cancer". Mamm. Genome. 16 (12): 942–54. doi:10.1007/s00335-005-0075-2. PMID16341674.
Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nat. Biotechnol. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID16964243.
Opitz B, Vinzing M, van Laak V, Schmeck B, Heine G, Günther S, Preissner R, Slevogt H, N'Guessan PD, Eitel J, Goldmann T, Flieger A, Suttorp N, Hippenstiel S (2007). "Legionella pneumophila induces IFNbeta in lung epithelial cells via IPS-1 and IRF3, which also control bacterial replication". J. Biol. Chem. 281 (47): 36173–9. doi:10.1074/jbc.M604638200. PMID16984921.
Hirata Y, Broquet AH, Menchén L, Kagnoff MF (2007). "Activation of innate immune defense mechanisms by signaling through RIG-I/IPS-1 in intestinal epithelial cells". J. Immunol. 179 (8): 5425–32. doi:10.4049/jimmunol.179.8.5425. PMID17911629.
Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, Du F, Ren J, Wu Y, Grishin N, Chen ZJ (2015). "Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation". Science. 347 (6227): aaa2630. doi:10.1126/science.aaa2630. PMID25636800.
