Source:http://linkedlifedata.com/resource/pubmed/id/16380379
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2006-2-20
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| pubmed:abstractText |
Virus-induced expression of interferon (IFN)-A genes is regulated by two members of the IFN regulatory factor (IRF) family, IRF-3 and IRF-7, which are activated by phosphorylation during viral infection by the IKK-related serine/threonine kinases TBK1 and IkappaB kinase epsilon (IKKepsilon). In this study, we demonstrate that three IRF-binding sites located in the virus-responsive element mediate the transcriptional activation of the IFN-A4 promoter by IRF-3. The precise arrangement of these IRF elements is required for synergistic activation of the IFN-A4 promoter following Newcastle disease virus infection or activation by TBK1 or IKKepsilon. The ordered assembly of IRF-3 multimers on the promoter also determines cooperative recruitment of IRF-3 and CREB-binding protein and differential virus-induced expression of IFN-A4 gene promoter compared with IFN-A11. Naturally occurring nucleotide substitutions disrupt two of the IRF elements in the IFN-A11 gene promoter, leading to a dramatic decrease in IRF-3 and CREB-binding protein recruitment and in IRF-3-dependent transcription. Transcription of the IFN-A4 promoter by IRF-7 is mediated by two IRF elements; promoter mutants that carry a reversed IRF element retain the ability to respond to IKKepsilon or TBK1 expression in the presence of IRF-7 but lose the capacity to respond to virus or kinase-induced IRF-3. Interestingly, IKKepsilon or TBK1 stimulates the IRF-7-mediated transcription of IFN-A11, although at a lesser extent compared with IFN-A4. Our data indicate that virus-induced expression of IFN-A genes is dictated by the organization of IRF elements within the IFN-A promoters and that the differential IFN-A gene expression, based on the IRF-3 responsiveness, is partially compensated in the presence of IRF-7 when both factors are activated by IKKepsilon or TBK1.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
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/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/TBK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tbk1 protein, mouse
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
24
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| pubmed:volume |
281
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4856-66
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16380379-Animals,
pubmed-meshheading:16380379-Base Sequence,
pubmed-meshheading:16380379-Binding Sites,
pubmed-meshheading:16380379-Cell Line,
pubmed-meshheading:16380379-Chromatin Immunoprecipitation,
pubmed-meshheading:16380379-Fibroblasts,
pubmed-meshheading:16380379-Gene Expression Regulation,
pubmed-meshheading:16380379-Gene Expression Regulation, Viral,
pubmed-meshheading:16380379-Genes, Reporter,
pubmed-meshheading:16380379-HeLa Cells,
pubmed-meshheading:16380379-Humans,
pubmed-meshheading:16380379-I-kappa B Kinase,
pubmed-meshheading:16380379-Immunoblotting,
pubmed-meshheading:16380379-Interferon Regulatory Factor-3,
pubmed-meshheading:16380379-Interferon Regulatory Factor-7,
pubmed-meshheading:16380379-Interferon-alpha,
pubmed-meshheading:16380379-Mice,
pubmed-meshheading:16380379-Molecular Sequence Data,
pubmed-meshheading:16380379-Mutation,
pubmed-meshheading:16380379-Plasmids,
pubmed-meshheading:16380379-Promoter Regions, Genetic,
pubmed-meshheading:16380379-Protein Binding,
pubmed-meshheading:16380379-Protein-Serine-Threonine Kinases,
pubmed-meshheading:16380379-Transcription, Genetic,
pubmed-meshheading:16380379-Transcriptional Activation,
pubmed-meshheading:16380379-Transfection
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| pubmed:year |
2006
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| pubmed:articleTitle |
Promoter organization of the interferon-A genes differentially affects virus-induced expression and responsiveness to TBK1 and IKKepsilon.
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| pubmed:affiliation |
UPR 2228-CNRS, Laboratoire de Régulation Transcriptionnelle et Maladies Génétiques, UFR Biomédicale des Saints-Pères, Université Paris V, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France. ahmet.civas@univ-paris5.fr
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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