| The human papillomavirus oncoprotein E7 attenuates NF-kappa B activation by targeting the Ikappa B kinase complex. | |
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MedLine Citation:
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PMID: 11986318 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Infection with high-risk human papillomaviruses (HPV) can lead to the development of cervical carcinomas. This process critically depends on the virus-encoded E6 and E7 oncoproteins, which stimulate proliferation by manipulating the function of a variety of host key regulatory proteins. Here we show that both viral proteins dose-dependently interfere with the transcriptional activity of NF-kappaB. A variety of experimental approaches revealed that a fraction of the E7 proteins is found in association with the IkappaB kinase complex and attenuates induced kinase activity of IkappaB kinase alpha (IKKalpha) and IKKbeta, thus resulting in impaired IkappaBalpha phosphorylation and degradation. Indirect immunofluorescence shows that E7 impairs TNFalpha-induced nuclear translocation of NF-kappaB, thus preventing NF-kappaB from binding to its cognate DNA. While E7 obviates IKK activation in the cytoplasm, the E6 protein reduces NF-kappaB p65-dependent transcriptional activity within the nucleus. We suggest that HPV oncogene-mediated suppression of NF-kappaB activity contributes to HPV escape from the immune system. |
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Authors:
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Dimitry Spitkovsky; Steffen P Hehner; Thomas G Hofmann; Andreas Möller; M Lienhard Schmitz |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2002-05-01 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 277 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-08 Completed Date: 2002-08-12 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 25576-82 Citation Subset: IM |
Affiliation:
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Institute for Vegetative Physiology, University of Cologne, Robert-Koch-Strasse 39, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line Electrophoretic Mobility Shift Assay Fluorescent Antibody Technique, Indirect Humans I-kappa B Kinase NF-kappa B / metabolism*, physiology Oncogene Proteins, Viral / physiology* Protein Transport Protein-Serine-Threonine Kinases / metabolism* Transcription, Genetic / physiology Tumor Necrosis Factor-alpha / metabolism |
| Chemical | |
Reg. No./Substance:
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0/NF-kappa B; 0/Oncogene Proteins, Viral; 0/Tumor Necrosis Factor-alpha; EC 2.7.1.-/IKBKE protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.10/CHUK protein, human; EC 2.7.11.10/I-kappa B Kinase; EC 2.7.11.10/IKBKB protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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