“MDA5”的意思、由来-开放百科全书

Function

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.^[1]

Clinical significance

Mutations in IFIH1/MDA5 are associated to {{SWL|type=mutations_associated_to|target=Singleton Merten Syndrome|label=Singleton-Merten Syndrome}}^[5] and to Aicardi–Goutières syndrome.

Antibodies against MDA5 are associated to amyopathic dermatomyositis with rapidly progressive interstitial lung disease.

References

1. ^¹{{cite web | title = Entrez Gene: IFIH1 interferon induced with helicase C domain 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64135| accessdate = }}
2. ^{{cite journal | vauthors = Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, Hiiragi A, Dermody TS, Fujita T, Akira S | title = Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5 | journal = The Journal of Experimental Medicine | volume = 205 | issue = 7 | pages = 1601–10 | date = July 2008 | pmid = 18591409 | pmc = 2442638 | doi = 10.1084/jem.20080091 }}
3. ^{{cite journal | vauthors = Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O | title = LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 4 | pages = 1512–7 | date = January 2010 | pmid = 20080593 | pmc = 2824407 | doi = 10.1073/pnas.0912986107 | bibcode = 2010PNAS..107.1512S }}
4. ^{{cite journal | vauthors = Takeuchi O, Akira S | title = MDA5/RIG-I and virus recognition | journal = Current Opinion in Immunology | volume = 20 | issue = 1 | pages = 17–22 | date = February 2008 | pmid = 18272355 | doi = 10.1016/j.coi.2008.01.002 }}
5. ^{{cite journal | vauthors = Rutsch F, MacDougall M, Lu C, Buers I, Mamaeva O, Nitschke Y, Rice GI, Erlandsen H, Kehl HG, Thiele H, Nürnberg P, Höhne W, Crow YJ, Feigenbaum A, Hennekam RC | title = A specific IFIH1 gain-of-function mutation causes Singleton-Merten syndrome | journal = American Journal of Human Genetics | volume = 96 | issue = 2 | pages = 275–82 | date = February 2015 | pmid = 25620204 | doi = 10.1016/j.ajhg.2014.12.014 | pmc=4320263}}

Further reading

{{cite journal | vauthors = Kang DC, Gopalkrishnan RV, Wu Q, Jankowsky E, Pyle AM, Fisher PB | title = mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 2 | pages = 637–42 | date = January 2002 | pmid = 11805321 | pmc = 117358 | doi = 10.1073/pnas.022637199 | bibcode = 2002PNAS...99..637K }}

{{cite journal | vauthors = Kovacsovics M, Martinon F, Micheau O, Bodmer JL, Hofmann K, Tschopp J | title = Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation | journal = Current Biology | volume = 12 | issue = 10 | pages = 838–43 | date = May 2002 | pmid = 12015121 | doi = 10.1016/S0960-9822(02)00842-4 }}

{{cite journal | vauthors = Cocude C, Truong MJ, Billaut-Mulot O, Delsart V, Darcissac E, Capron A, Mouton Y, Bahr GM | title = A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication | journal = The Journal of General Virology | volume = 84 | issue = Pt 12 | pages = 3215–25 | date = December 2003 | pmid = 14645903 | doi = 10.1099/vir.0.19300-0 }}

{{cite journal | vauthors = Kang DC, Gopalkrishnan RV, Lin L, Randolph A, Valerie K, Pestka S, Fisher PB | title = Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene | journal = Oncogene | volume = 23 | issue = 9 | pages = 1789–800 | date = March 2004 | pmid = 14676839 | doi = 10.1038/sj.onc.1207300 }}

{{cite journal | vauthors = Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S, Randall RE | title = The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 49 | pages = 17264–9 | date = December 2004 | pmid = 15563593 | pmc = 535396 | doi = 10.1073/pnas.0407639101 | bibcode = 2004PNAS..10117264A }}

{{cite journal | vauthors = Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M, Akira S, Yonehara S, Kato A, Fujita T | title = Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity | journal = Journal of Immunology | volume = 175 | issue = 5 | pages = 2851–8 | date = September 2005 | pmid = 16116171 | doi = 10.4049/jimmunol.175.5.2851 }}

{{cite journal | vauthors = Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S | title = IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction | journal = Nature Immunology | volume = 6 | issue = 10 | pages = 981–8 | date = October 2005 | pmid = 16127453 | doi = 10.1038/ni1243 }}

{{cite journal | vauthors = Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J | title = Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus | journal = Nature | volume = 437 | issue = 7062 | pages = 1167–72 | date = October 2005 | pmid = 16177806 | doi = 10.1038/nature04193 | bibcode = 2005Natur.437.1167M }}

{{cite journal | vauthors = Lin L, Su Z, Lebedeva IV, Gupta P, Boukerche H, Rai T, Barber GN, Dent P, Sarkar D, Fisher PB | title = Activation of Ras/Raf protects cells from melanoma differentiation-associated gene-5-induced apoptosis | journal = Cell Death and Differentiation | volume = 13 | issue = 11 | pages = 1982–93 | date = November 2006 | pmid = 16575407 | doi = 10.1038/sj.cdd.4401899 }}

{{cite journal | vauthors = Smyth DJ, Cooper JD, Bailey R, Field S, Burren O, Smink LJ, Guja C, Ionescu-Tirgoviste C, Widmer B, Dunger DB, Savage DA, Walker NM, Clayton DG, Todd JA | title = A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region | journal = Nature Genetics | volume = 38 | issue = 6 | pages = 617–9 | date = June 2006 | pmid = 16699517 | doi = 10.1038/ng1800 }}

{{cite journal | vauthors = Berghäll H, Sirén J, Sarkar D, Julkunen I, Fisher PB, Vainionpää R, Matikainen S | title = The interferon-inducible RNA helicase, mda-5, is involved in measles virus-induced expression of antiviral cytokines | journal = Microbes and Infection | volume = 8 | issue = 8 | pages = 2138–44 | date = July 2006 | pmid = 16782388 | doi = 10.1016/j.micinf.2006.04.005 }}

{{cite journal | vauthors = Sirén J, Imaizumi T, Sarkar D, Pietilä T, Noah DL, Lin R, Hiscott J, Krug RM, Fisher PB, Julkunen I, Matikainen S | title = Retinoic acid inducible gene-I and mda-5 are involved in influenza A virus-induced expression of antiviral cytokines | journal = Microbes and Infection | volume = 8 | issue = 8 | pages = 2013–20 | date = July 2006 | pmid = 16797201 | doi = 10.1016/j.micinf.2006.02.028 }}

{{cite journal | vauthors = Barral PM, Morrison JM, Drahos J, Gupta P, Sarkar D, Fisher PB, Racaniello VR | title = MDA-5 is cleaved in poliovirus-infected cells | journal = Journal of Virology | volume = 81 | issue = 8 | pages = 3677–84 | date = April 2007 | pmid = 17267501 | pmc = 1866155 | doi = 10.1128/JVI.01360-06 }}

{{cite journal | vauthors = Marinou I, Montgomery DS, Dickson MC, Binks MH, Moore DJ, Bax DE, Wilson AG | title = The interferon induced with helicase domain 1 A946T polymorphism is not associated with rheumatoid arthritis | journal = Arthritis Research & Therapy | volume = 9 | issue = 2 | pages = R40 | year = 2007 | pmid = 17442111 | pmc = 1906818 | doi = 10.1186/ar2179 }}

{{cite journal | vauthors = Sutherland A, Davies J, Owen CJ, Vaikkakara S, Walker C, Cheetham TD, James RA, Perros P, Donaldson PT, Cordell HJ, Quinton R, Pearce SH | title = Genomic polymorphism at the interferon-induced helicase (IFIH1) locus contributes to Graves' disease susceptibility | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 92 | issue = 8 | pages = 3338–41 | date = August 2007 | pmid = 17535987 | doi = 10.1210/jc.2007-0173 }}

{{cite journal | vauthors = Matsukura S, Kokubu F, Kurokawa M, Kawaguchi M, Ieki K, Kuga H, Odaka M, Suzuki S, Watanabe S, Homma T, Takeuchi H, Nohtomi K, Adachi M | title = Role of RIG-I, MDA-5, and PKR on the expression of inflammatory chemokines induced by synthetic dsRNA in airway epithelial cells | journal = International Archives of Allergy and Immunology | volume = 143 Suppl 1 | issue = | pages = 80–3 | year = 2007 | pmid = 17541283 | doi = 10.1159/000101411 }}

2 : RIG-I-like receptors|Intracellular receptors