P53 represses human papillomavirus type 16 DNA replication via the viral E2 protein

Virology Journal
C BrownK Gaston

Abstract

Human papillomavirus (HPV) DNA replication can be inhibited by the cellular tumour suppressor protein p53. However, the mechanism through which p53 inhibits viral replication and the role that this might play in the HPV life cycle are not known. The papillomavirus E2 protein is required for efficient HPV DNA replication and also regulates viral gene expression. E2 represses transcription of the HPV E6 and E7 oncogenes and can thereby modulate indirectly host cell proliferation and survival. In addition, the E2 protein from HPV 16 has been shown to bind p53 and to be capable of inducing apoptosis independently of E6 and E7. Here we use a panel of E2 mutants to confirm that mutations which block the induction of apoptosis via this E6/E7-independent pathway, have little or no effect on the induction of apoptosis by the E6/E7-dependent pathway. Although these mutations in E2 do not affect the ability of the protein to mediate HPV DNA replication, they do abrogate the repressive effects of p53 on the transcriptional activity of E2 and prevent the inhibition of E2-dependent HPV DNA replication by p53. These data suggest that p53 down-regulates HPV 16 DNA replication via the E2 protein.

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Citations

Dec 25, 2012·Archives of Gynecology and Obstetrics·Qiong CaiAiping Dian
Apr 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Eun-Young KhoLouise T Chow
May 27, 2015·Viruses·Caleb C McKinneyAlison A McBride
Nov 19, 2013·Tropical Medicine & International Health : TM & IH·Stephen GichuhiMatthew J Burton
Jul 5, 2011·Reviews in Medical Virology·Pedro A Lazo, Claudio R Santos
Jun 18, 2010·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Louise T ChowBettie M Steinberg
Jul 16, 2013·Virology·Alison A McBride
Aug 16, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yue Ma-LauerAlbrecht von Brunn
Feb 1, 2020·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Josephine Raun HenriksenSteffen Heegaard
Oct 18, 2011·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Amnon Amir, Or Zuk

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