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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2004-4-6
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pubmed:abstractText |
Toll-like receptor-3 is critically involved in host defense against viruses through induction of type I interferons (IFNs). Recent studies suggest that a Toll/interleukin-1 receptor domain-containing adapter protein (TRIF) and two protein kinases (TANK-binding kinase-1 (TBK1) and IkappaB kinase (IKK)-epsilon) are critically involved in Toll-like receptor-3-mediated IFN-beta production through activation of IFN regulatory factor (IRF)-3 and IRF-7. In this study, we demonstrate that TRIF interacts with both IRF-7 and IRF-3. In addition to TBK1 and IKKepsilon, our results indicate that IKKbeta can also phosphorylate IRF-3 and activate the IFN-stimulated response element. TRIF-induced IRF-3 and IRF-7 activation was mediated by TBK1 and its downstream kinases IKKbeta and IKKepsilon. TRIF induced NF-kappaB activation through an IKKbeta- and tumor necrosis factor receptor-associated factor-6-dependent (but not TBK1- and IKKepsilon-dependent) pathway. In addition, TRIF also induced apoptosis through a RIP/FADD/caspase-8-dependent and mitochondrion-independent pathway. Furthermore, our results suggest that the TRIF-induced IFN-stimulated response element and NF-kappaB activation and apoptosis pathways are uncoupled and provide a molecular explanation for the divergent effects induced by the adapter protein TRIF.
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pubmed:grant |
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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, Vesicular...,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CHUK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Casp8 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKE protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IRF3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IRF7 protein, human,
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/Interferons,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TBK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TICAM-1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 6,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15652-61
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14739303-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:14739303-Animals,
pubmed-meshheading:14739303-Apoptosis,
pubmed-meshheading:14739303-Blotting, Western,
pubmed-meshheading:14739303-Caspase 8,
pubmed-meshheading:14739303-Caspases,
pubmed-meshheading:14739303-Cell Line,
pubmed-meshheading:14739303-DNA Fragmentation,
pubmed-meshheading:14739303-DNA-Binding Proteins,
pubmed-meshheading:14739303-Gene Library,
pubmed-meshheading:14739303-Genes, Reporter,
pubmed-meshheading:14739303-Genetic Vectors,
pubmed-meshheading:14739303-Humans,
pubmed-meshheading:14739303-I-kappa B Kinase,
pubmed-meshheading:14739303-Interferon Regulatory Factor-3,
pubmed-meshheading:14739303-Interferon Regulatory Factor-7,
pubmed-meshheading:14739303-Interferons,
pubmed-meshheading:14739303-Models, Biological,
pubmed-meshheading:14739303-Models, Genetic,
pubmed-meshheading:14739303-NF-kappa B,
pubmed-meshheading:14739303-Phosphorylation,
pubmed-meshheading:14739303-Plasmids,
pubmed-meshheading:14739303-Precipitin Tests,
pubmed-meshheading:14739303-Protein Structure, Tertiary,
pubmed-meshheading:14739303-Protein-Serine-Threonine Kinases,
pubmed-meshheading:14739303-Proteins,
pubmed-meshheading:14739303-Response Elements,
pubmed-meshheading:14739303-Sendai virus,
pubmed-meshheading:14739303-Signal Transduction,
pubmed-meshheading:14739303-TNF Receptor-Associated Factor 6,
pubmed-meshheading:14739303-Transcription Factors,
pubmed-meshheading:14739303-Transfection,
pubmed-meshheading:14739303-Two-Hybrid System Techniques
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pubmed:year |
2004
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pubmed:articleTitle |
Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways.
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pubmed:affiliation |
Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, Colorado 80206, USA. shuh@njc.org
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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