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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2006-8-17
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pubmed:abstractText |
The induction of type I interferon (IFN) and the development of the innate antiviral response are mediated by the activation of interferon regulatory factor (IRF)-3 and IRF-7 under the control of the non-canonical kinases TBK-1 and IKKepsilon. The initial sensing of infection by RNA viruses is mediated by the cytoplasmic, retinoic acid inducible gene I (RIG-I), via a Toll-like receptor (TLR) independent signaling pathway. In the present study, we identify key residues involved in IRF-3 and IRF-7 phosphorylation using TAP-tag purification of TBK-1 and IKKepsilon proteins. Based on the identification of an extended sequence motif--SxSxxxS--common to both IRF-3 and IRF-7, an IRF-7 pSer477/479 phosphospecific antibody was generated. Virus infection, TBK-1/IKKepsilon expression or co-expression of different signaling adaptors such as RIG-I, MAVS and TRIF, all stimulated pSer477/479 phosphorylation. Furthermore, the newly identified adaptor of the RIG-I pathway (MAVS/IPS-1/VISA/Cardif) was able to induce IRF and NF-kappaB dependent promoter activity as efficiently as the constitutively active form of RIG-I (DeltaRIG-I). Co-expression of the NS3/4A protease activity of hepatitis C virus however blocked MAVS-mediated gene activation in a dose dependent manner. These studies link RIG-I sensing of viral RNA to downstream kinase signaling and phosphorylation of IRF-3 and IRF-7 via the MAVS/IPS/VISA/Cardif adaptor.
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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/Adaptor Proteins, Signal Transducing,
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/Interferon Inducers,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-7,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B p50 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/NFKB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NS3 protein, hepatitis C virus,
http://linkedlifedata.com/resource/pubmed/chemical/NS4 protein, hepatitis C virus,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/TBK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/VISA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Nonstructural Proteins
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pubmed:status |
MEDLINE
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pubmed:issn |
1165-158X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17-28
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16914100-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:16914100-Antibody Specificity,
pubmed-meshheading:16914100-Cell Nucleus,
pubmed-meshheading:16914100-Cells, Cultured,
pubmed-meshheading:16914100-DEAD-box RNA Helicases,
pubmed-meshheading:16914100-Flaviviridae Infections,
pubmed-meshheading:16914100-Gene Expression Regulation,
pubmed-meshheading:16914100-Hepacivirus,
pubmed-meshheading:16914100-Humans,
pubmed-meshheading:16914100-I-kappa B Kinase,
pubmed-meshheading:16914100-Immunity, Innate,
pubmed-meshheading:16914100-Interferon Inducers,
pubmed-meshheading:16914100-Interferon Regulatory Factor-3,
pubmed-meshheading:16914100-Interferon Regulatory Factor-7,
pubmed-meshheading:16914100-Interferon-alpha,
pubmed-meshheading:16914100-Interferon-beta,
pubmed-meshheading:16914100-Mitochondrial Proteins,
pubmed-meshheading:16914100-Models, Biological,
pubmed-meshheading:16914100-NF-kappa B p50 Subunit,
pubmed-meshheading:16914100-Phosphorylation,
pubmed-meshheading:16914100-Promoter Regions, Genetic,
pubmed-meshheading:16914100-Protein Binding,
pubmed-meshheading:16914100-Protein Structure, Tertiary,
pubmed-meshheading:16914100-Protein-Serine-Threonine Kinases,
pubmed-meshheading:16914100-RNA Helicases,
pubmed-meshheading:16914100-Response Elements,
pubmed-meshheading:16914100-Signal Transduction,
pubmed-meshheading:16914100-Substrate Specificity,
pubmed-meshheading:16914100-Transcriptional Activation,
pubmed-meshheading:16914100-Transfection,
pubmed-meshheading:16914100-Viral Nonstructural Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
Induction of IRF-3 and IRF-7 phosphorylation following activation of the RIG-I pathway.
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pubmed:affiliation |
Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, 3755 Cote Ste. Catherine, Montreal, Quebec, Canada H3T 1E2.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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