UMMS Affiliation

University of Massachusetts Medical School

Publication Date

10-19-2007

Document Type

Article

Subjects

Cells, Cultured; Chromatin Immunoprecipitation; Human papillomavirus 16; Humans; Keratinocytes; Mutant Proteins; Oncogene Proteins, Viral; Promoter Regions (Genetics); Protein Binding; Repressor Proteins; Telomerase; Ubiquitin-Protein Ligases

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The human papillomavirus (HPV) type 16 (HPV16) E6 protein stimulates transcription of the catalytic subunit of telomerase, hTERT, in epithelial cells. It has been reported that binding to the ubiquitin ligase E6AP is required for this E6 activity, with E6 directing E6AP to the hTERT promoter. We previously reported two E6AP binding-defective HPV16 E6 mutations that induced immortalization of human mammary epithelial cells. Because activation of hTERT is proposed to be necessary for epithelial cell immortalization, we sought to further characterize the relationship between E6/E6AP association and telomerase induction. We demonstrate that while these E6 mutants do not bind E6AP, they retain the capability to stimulate the expression of hTERT. Chromatin immunoprecipitation assays confirmed the presence of Myc, wild-type E6, and the E6AP binding-defective E6 mutants, but not E6AP itself, at the endogenous hTERT promoter. Interestingly, an immortalization-defective E6 mutant localized to the hTERT promoter but failed to increase transcription. We conclude that binding to E6AP is not necessary for E6 localization to or activation of the hTERT promoter and that another activity of E6 is involved in hTERT activation.

Rights and Permissions

Citation: J Virol. 2008 Jan;82(1):71-6. Epub 2007 Oct 17. Link to article on publisher's site

DOI of Published Version

10.1128/JVI.01776-07

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Journal of virology

PubMed ID

17942561

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