Activated Notch1 Inhibits p53-Induced Apoptosis and Sustains Transformation by Human Papillomavirus Type 16 E6 and E7 Oncogenes through a PI3K-PKB/Akt-Dependent Pathway

Nair, Pradip and Somasundaram, Kumaravel and Krishna, Sudhir (2003) Activated Notch1 Inhibits p53-Induced Apoptosis and Sustains Transformation by Human Papillomavirus Type 16 E6 and E7 Oncogenes through a PI3K-PKB/Akt-Dependent Pathway. In: Journal of Virology, 77 (12). pp. 7106-7112.

PDF 7106.pdf - Published Version Restricted to Registered users only Download (1MB) | Request a copy

Abstract

Activated Notch1 (AcN1) alleles cooperate with oncogenes from DNA tumor viruses in transformation of epithelial cells. AcN1 signaling has pleiotropic effects, and suggested oncogenic roles include driving proliferation through cyclin D1 or the generation of resistance to apoptosis on matrix withdrawal through sphatidylinositol 3-kinase (PI3K)-PKB/Akt-dependent pathway. Here, we extend the antiapoptotic role for AcN1 by showing inhibition of p53-induced apoptosis and transactivation. Chemical inhibitors of the PI3K pathway block AcN1-induced inhibition of p53-dependent apoptosis and nuclear localization of Hdm2. We show that expression of wild-type p53 does not inhibit synergistic transformation by AcN1 and human papillomavirus E6 and E7 oncogenes. We suggest that activation of Notch signaling may serve as an additional mechanism to inhibit wild-type p53 function in papillomavirus-associated neoplasia.

Item Type:	Journal Article
Publication:	Journal of Virology
Publisher:	American Society for Microbiology.
Additional Information:	Copyright of this article belongs to American Society for Microbiology.
Keywords:	Tumor-Suppressor P53;Neoplastic Lesions;Cells;Oncoprotein;Akt; Expression;Mdm2;Phosphoryalation;Stabilization
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	02 Dec 2008 09:33
Last Modified:	08 Jul 2011 09:10
URI:	http://eprints.iisc.ac.in/id/eprint/16571

Actions (login required)

View Item