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J. Virol. doi:10.1128/JVI.01776-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Binding of HPV 16 E6 to E6AP is not required for activation of hTERT

Department of Medicine University of Massachusetts Medical School

^* To whom correspondence should be addressed. Email: elliot.androphy{at}umassmed.edu.

	Abstract

The human papillomavirus (HPV) type 16 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 (MECs). 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 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.

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