p53 levels in human mammary epithelial cells expressing wild-type and mutant human papillomavirus type 16 (HPV-16) E6 proteins

1996 ◽  
Author(s):  
S Holt ◽  
L Gollahon ◽  
T Willingham ◽  
M Barbosa ◽  
J Shay
Keyword(s):  
Human Papillomavirus ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Wild Type ◽  
Hpv 16 ◽  
Human Mammary Epithelial Cells ◽  
Human Papillomavirus Type 16 ◽  
Human Mammary Epithelial

scholarly journals Human Papillomavirus Type 16 E6-Induced Degradation of E6TP1 Correlates with Its Ability To Immortalize Human Mammary Epithelial Cells

2001 ◽  
Vol 75 (9) ◽  
pp. 4459-4466 ◽  
Author(s):  
Qingshen Gao ◽  
Latika Singh ◽  
Ajay Kumar ◽  
Seetha Srinivasan ◽  
David E. Wazer ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Cellular Transformation ◽  
Mammary Epithelial ◽  
Human Mammary Epithelial Cells ◽  
Human Papillomavirus Type 16 ◽  
Human Mammary Epithelial ◽  
E6 Protein

ABSTRACT Recent analyses have identified a number of binding partners for E6, including E6AP, ERC55, paxillin, hDlg, p300, interferon regulatory factor 3, hMCM7, Bak, and E6TP1. Notably, association with E6 targets p53, E6TP1, myc, hMCM7, and Bak for degradation. However, the relative importance of the various E6 targets in cellular transformation remains unclear. E6 alone can dominantly immortalize normal human mammary epithelial cells (MECs), permitting an assessment of the importance of various E6 targets in cellular transformation. Studies in this system indicate that E6-induced degradation of p53 and E6 binding to ERC55 or hDlg do not correlate with efficient immortalization. Here, we have examined the role of E6TP1, a Rap GTPase-activating protein, in E6-induced immortalization of MECs. We tested a large set of human papillomavirus type 16 E6 mutants for their ability to bind and target E6TP1 for degradation in vitro and in vivo. We observed a strict correlation between the ability of E6 protein to target E6TP1 for degradation and its ability to immortalize MECs. Recent studies have identified telomerase as a target of E6 protein. Previous analyses of E6 mutants have revealed this trait to closely correlate with MEC immortalization. We examined our entire panel of E6 mutants for rapid induction of telomerase activity and found in general a strong correlation with immortalizing ability. The tight correlation between E6TP1 degradation and MEC immortalization strongly supports a critical role of functional inactivation of E6TP1 in E6-induced cellular immortalization.

scholarly journals Binding of Human Papillomavirus Type 16 E6 to E6AP Is Not Required for Activation of hTERT

2007 ◽  
Vol 82 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Pedja Sekaric ◽  
Jonathan J. Cherry ◽  
Elliot J. Androphy
Keyword(s):  
Human Papillomavirus ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Htert Promoter ◽  
Hpv16 E6 ◽  
Human Papillomavirus Type 16 ◽  
Human Mammary Epithelial ◽  
E6 Protein ◽  
The Relationship

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.

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