Binding of human papillomavirus type 16 E6 to E6AP is not required for activation of hTERT

Pedja Sekaric, Jonathan J. Cherry, Elliot Androphy

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)71-76
Number of pages6
JournalJournal of Virology
Volume82
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

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Human papillomavirus 16
Papillomaviridae
Telomerase
Epithelial Cells
promoter regions
telomerase
epithelial cells
mutants
transcription (genetics)
Chromatin Immunoprecipitation
Ligases
Ubiquitin
Breast
protein subunits
ubiquitin
ligases
mutagenesis
breasts
chromatin
Mutation

ASJC Scopus subject areas

  • Immunology

Cite this

Binding of human papillomavirus type 16 E6 to E6AP is not required for activation of hTERT. / Sekaric, Pedja; Cherry, Jonathan J.; Androphy, Elliot.

In: Journal of Virology, Vol. 82, No. 1, 01.2008, p. 71-76.

Research output: Contribution to journalArticle

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