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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2010-4-20
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pubmed:abstractText |
RIG-I detects invading viral RNA and activates the transcription factors NF-kappaB and IRF3 through the mitochondrial protein MAVS. Here we show that RNA bearing 5'-triphosphate strongly activates the RIG-I-IRF3 signaling cascade in a reconstituted system composed of RIG-I, mitochondria, and cytosol. Activation of RIG-I requires not only RNA but also polyubiquitin chains linked through lysine 63 (K63) of ubiquitin. RIG-I binds specifically to K63-polyubiquitin chains through its tandem CARD domains in a manner that depends on RNA and ATP. Mutations in the CARD domains that abrogate ubiquitin binding also impair RIG-I activation. Remarkably, unanchored K63-ubiquitin chains, which are not conjugated to any target protein, potently activate RIG-I. These ubiquitin chains function as an endogenous ligand of RIG-I in human cells. Our results delineate the mechanism of RIG-I activation, identify CARD domains as a ubiquitin sensor, and demonstrate that unanchored K63-polyubiquitin chains are signaling molecules in antiviral innate immunity.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/DDX58 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/DEAD-box RNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/IRF3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/Polyphosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Polyubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Double-Stranded,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/TRIM25 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/UBE2N protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Conjugating Enzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/triphosphoric acid
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1097-4172
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
141
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
315-30
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:20403326-Adenosine Triphosphate,
pubmed-meshheading:20403326-Cell Line,
pubmed-meshheading:20403326-DEAD-box RNA Helicases,
pubmed-meshheading:20403326-Humans,
pubmed-meshheading:20403326-I-kappa B Kinase,
pubmed-meshheading:20403326-Immunity, Innate,
pubmed-meshheading:20403326-Interferon Regulatory Factor-3,
pubmed-meshheading:20403326-Polyphosphates,
pubmed-meshheading:20403326-Polyubiquitin,
pubmed-meshheading:20403326-RNA, Double-Stranded,
pubmed-meshheading:20403326-RNA, Viral,
pubmed-meshheading:20403326-Signal Transduction,
pubmed-meshheading:20403326-Transcription Factors,
pubmed-meshheading:20403326-Ubiquitin-Conjugating Enzymes,
pubmed-meshheading:20403326-Ubiquitin-Protein Ligases
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pubmed:year |
2010
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pubmed:articleTitle |
Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity.
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pubmed:affiliation |
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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