| Regulation of human papillomavirus type 16 E7 activity through direct protein interaction with the E2 transcriptional activator. | |
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MedLine Citation:
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PMID: 16439535 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In order to ensure a productive life cycle, human papillomaviruses (HPVs) require fine regulation of their gene products. Uncontrolled activity of the viral oncoproteins E6 and E7 results in the immortalization of the infected epithelial cells and thus prevents the production of mature virions. Ectopically expressed E2 has been shown to suppress transcription of the HPV E6 and E7 region in cell lines where the viral DNA is integrated into the host genome, resulting in growth inhibition. However, it has been demonstrated that growth control of these cell lines can also occur independently of HPV E2 transcriptional activity in high-risk HPV types. In addition, E2 is unable to suppress transcription of the same region in cell lines derived from cervical tumors that harbor only episomal copies of the viral DNA. Here we show that HPV type 16 (HPV-16) E2 is capable of inhibiting HPV-16 E7 cooperation with an activated ras oncogene in the transformation of primary rodent cells. Furthermore, we demonstrate a direct interaction between the E2 and E7 proteins which requires the hinge region of E2 and the zinc-binding domain of E7. These viral proteins interact in vivo, and E2 has a marked effect upon both the stability of E7 and its cellular location, where it is responsible for recruiting E7 onto mitotic chromosomes at the later stages of mitosis. These results demonstrate a direct role for E2 in regulating the function of E7 and suggest an important role for E2 in directing E7 localization during mitosis. |
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Authors:
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Noor Gammoh; Helena Sterlinko Grm; Paola Massimi; Lawrence Banks |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of virology Volume: 80 ISSN: 0022-538X ISO Abbreviation: J. Virol. Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-01-27 Completed Date: 2006-02-24 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 1787-97 Citation Subset: IM |
Affiliation:
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International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste 34012, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Cell Transformation, Viral Chromosomes, Mammalian / metabolism DNA / metabolism DNA-Binding Proteins / metabolism* Humans Immunohistochemistry Microscopy, Confocal Oncogene Proteins, Viral / metabolism* Papillomaviridae / physiology* Protein Binding Protein Interaction Mapping Protein Structure, Tertiary Rats Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/E2 protein, Human papillomavirus type 16; 0/Oncogene Proteins, Viral; 0/oncogene protein E7, Human papillomavirus type 16; 9007-49-2/DNA |
| Comments/Corrections | |
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