MDA5 (Melanoma Differentiation-Associated protein 5) is a RIG-I-like receptordsRNAhelicaseenzyme that in humans is encoded by the IFIH1gene. MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor (recognizing dsRNA) that is a sensor for viruses. MDA5 typically recognizes dsRNA that is over 2000nts in length. For many viruses, effective MDA5-mediated antiviral responses are dependent on functionally active LGP2. The signaling cascades in MDA5 is initiated via CARD domain.
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein that is upregulated in response to treatment with beta-interferon (IFNB) and a protein kinase C-activating compound, mezerein (MEZ). Irreversible reprogramming of melanomas can be achieved by treatment with both these agents; treatment with either agent alone only achieves reversible differentiation.
^Rutsch, F; MacDougall, M; Lu, C; Buers, I; Mamaeva, O; Nitschke, Y; Rice, G. I.; Erlandsen, H; Kehl, H. G.; Thiele, H; Nürnberg, P; Höhne, W; Crow, Y. J.; Feigenbaum, A; Hennekam, R. C. (2015). "A Specific IFIH1 Gain-of-function Mutation Causes Singleton-Merten Syndrome". The American Journal of Human Genetics96: 275–82. doi:10.1016/j.ajhg.2014.12.014. PMID25620204.
Kovacsovics M, Martinon F, Micheau O et al. (2002). "Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation". Curr. Biol.12 (10): 838–843. doi:10.1016/S0960-9822(02)00842-4. PMID12015121.
Cocude C, Truong MJ, Billaut-Mulot O et al. (2004). "A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication". J. Gen. Virol.84 (Pt 12): 3215–3225. doi:10.1099/vir.0.19300-0. PMID14645903.
Kang DC, Gopalkrishnan RV, Lin L et al. (2004). "Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene". Oncogene23 (9): 1789–1800. doi:10.1038/sj.onc.1207300. PMID14676839.
Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet.36 (1): 40–45. doi:10.1038/ng1285. PMID14702039.
Yoneyama M, Kikuchi M, Matsumoto K et al. (2005). "Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity". J. Immunol.175 (5): 2851–8. doi:10.4049/jimmunol.175.5.2851. PMID16116171.
Kawai T, Takahashi K, Sato S et al. (2005). "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction". Nat. Immunol.6 (10): 981–988. doi:10.1038/ni1243. PMID16127453.
Meylan E, Curran J, Hofmann K et al. (2005). "Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus". Nature437 (7062): 1167–1172. doi:10.1038/nature04193. PMID16177806.
Lin L, Su Z, Lebedeva IV et al. (2006). "Activation of Ras/Raf protects cells from melanoma differentiation-associated gene-5-induced apoptosis". Cell Death Differ.13 (11): 1982–1993. doi:10.1038/sj.cdd.4401899. PMID16575407.
Smyth DJ, Cooper JD, Bailey R et al. (2006). "A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region". Nat. Genet.38 (6): 617–619. doi:10.1038/ng1800. PMID16699517.
Berghäll H, Sirén J, Sarkar D et al. (2007). "The interferon-inducible RNA helicase, mda-5, is involved in measles virus-induced expression of antiviral cytokines". Microbes Infect.8 (8): 2138–2144. doi:10.1016/j.micinf.2006.04.005. PMID16782388.
Sirén J, Imaizumi T, Sarkar D et al. (2007). "Retinoic acid inducible gene-I and mda-5 are involved in influenza A virus-induced expression of antiviral cytokines". Microbes Infect.8 (8): 2013–2020. doi:10.1016/j.micinf.2006.02.028. PMID16797201.
Sutherland A, Davies J, Owen CJ et al. (2007). "Genomic polymorphism at the interferon-induced helicase (IFIH1) locus contributes to Graves' disease susceptibility". J. Clin. Endocrinol. Metab.92 (8): 3338–3341. doi:10.1210/jc.2007-0173. PMID17535987.
Matsukura S, Kokubu F, Kurokawa M et al. (2007). "Role of RIG-I, MDA-5, and PKR on the expression of inflammatory chemokines induced by synthetic dsRNA in airway epithelial cells". Int. Arch. Allergy Immunol. 143 Suppl 1: 80–83. doi:10.1159/000101411. PMID17541283.