The E7 Proteins of Low- and High-risk Human Papillomaviruses Share the Ability to Target the Prb Family Member P130 for Degradation.
From: Department of Microbiology and Immunology and The Walther Oncology Center, Indiana University School of Medicine and The Walther Cancer Institute, Indianapolis, IN 46202, USA.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Jan 2006
- ISSN: 0027-8424
- Volume: 103
- Issue: 2
- Pages: 437-42
- Medium: Print
- Language: English
- Citation (JAMA): Zhang Benyue, Chen Wei, Roman Ann, et al. The E7 Proteins of Low- and High-risk Human Papillomaviruses Share the Ability to Target the Prb Family Member P130 for Degradation.. Proc. Natl. Acad. Sci. U.S.A. Jan 2006;103:437-42
Abstract
High-risk human papillomaviruses (HPVs) (e.g., HPV-16) cause anogenital and head and neck cancers, and low-risk HPVs (e.g., HPV-6) cause benign hyperproliferative disease. The E7 protein of HPV-16 binds all retinoblastoma tumor suppressor protein (pRB) family members with higher affinity than HPV-6E7. The HPV-16 E7 protein has been reported to target pRB family members for degradation and to immortalize cells. Here we tested the hypothesis that the low-risk E7 protein has an intrinsic ability to decrease expression of pRB family members. First, we introduced a high-affinity pRB-binding site into HPV-6 E7 (6E7G22D) and showed that, in human foreskin keratinocytes, HPV-6 E7G22D decreased the level of pRB protein but not pRB mRNA. Second, we analyzed the ability of wild-type HPV-6 E7 to destabilize the other pRB family members, p107 and p130. HPV-6 E7, like HPV-16 E7, decreased the level of p130 protein. This decrease was inhibited by MG132, a proteasome inhibitor. Binding of HPV-6 E7 to p130 was necessary but not sufficient to decrease the level of p130. Furthermore, the destabilization of p130 correlated with a decrease in the expression of involucrin, a differentiation marker. We suggest that the shared activity of HPV-16 E7 and HPV-6 E7 to destabilize p130 and decrease or delay differentiation may be related to the role of E7 in the HPV life cycle. The added ability of HPV-16 E7 to regulate pRB and p107 may be related to oncogenic activity.
Mesh Headings (Keywords): Amino Acid Sequence, Binding Sites, Cell Differentiation, Cells, Cultured, Culture Media, Humans, Keratinocytes, Molecular Sequence Data, Oncogene Proteins, Viral, Papillomaviridae, Proteasome Endopeptidase Complex, Retinoblastoma-Like Protein p130, Risk Factors
Check for Full Text / PubMed Unique Identifier (PMID): 16381817
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