Source:http://linkedlifedata.com/resource/pubmed/id/15664159
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2005-1-24
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| pubmed:abstractText |
Many viruses encode proteins that counteract the development of the interferon (IFN)-mediated antiviral state. Here, we report that interferon regulatory factor 7 (IRF7), a key mediator of type I IFN induction, is targeted for degradation by binding to the RTA immediate-early nuclear transcription factor encoded by Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8). Cotransfection with RTA blocked IRF7-mediated IFNalpha and IFNbeta mRNA production and promoted the ubiquitination and degradation of IRF7 protein in a proteasome-dependent fashion. Addition of RTA also promoted polyubiquitination of IRF7 in an in vitro cell free assay, demonstrating that RTA itself acts as a ubiquitin E3 ligase. RTA also autoregulated its own polyubiquitination and stability, and both activities were abolished by point mutations in a Cys plus His-rich N-terminal domain. Therefore, manipulation of the stability and function of IRF7 by the KSHV RTA transcription factor provides an unexpected regulatory strategy for circumventing the innate immune defence system.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/IRF7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-7,
http://linkedlifedata.com/resource/pubmed/chemical/ORF 50 transactivator,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
1074-7613
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
22
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
59-70
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:15664159-DNA-Binding Proteins,
pubmed-meshheading:15664159-Gene Expression Regulation, Viral,
pubmed-meshheading:15664159-Genetic Vectors,
pubmed-meshheading:15664159-HeLa Cells,
pubmed-meshheading:15664159-Herpesvirus 8, Human,
pubmed-meshheading:15664159-Humans,
pubmed-meshheading:15664159-Interferon Regulatory Factor-7,
pubmed-meshheading:15664159-Mutagenesis, Site-Directed,
pubmed-meshheading:15664159-Phosphorylation,
pubmed-meshheading:15664159-Plasmids,
pubmed-meshheading:15664159-Promoter Regions, Genetic,
pubmed-meshheading:15664159-Protein Binding,
pubmed-meshheading:15664159-Substrate Specificity,
pubmed-meshheading:15664159-Trans-Activators,
pubmed-meshheading:15664159-Transfection,
pubmed-meshheading:15664159-Tumor Cells, Cultured,
pubmed-meshheading:15664159-Ubiquitin-Protein Ligases,
pubmed-meshheading:15664159-Virus Activation
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| pubmed:year |
2005
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| pubmed:articleTitle |
The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation.
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| pubmed:affiliation |
Molecular Virology Laboratories, Viral Oncology Program, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, MD 2123, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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