p53 represses human papillomavirus type 16 DNA replication via the viral E2 protein

Craig Brown¹ , Anna M Kowalczyk¹ , Ewan R Taylor² , Iain M Morgan² and Kevin Gaston¹

¹Department of Biochemistry, School of Medical School, University of Bristol, Bristol, UK

²Institute of Comparative Medicine, University of Glasgow, Glasgow, UK

author email corresponding author email

Virology Journal 2008, 5:5doi:10.1186/1743-422X-5-5


Published:	11 January 2008

Abstract

Background

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.

Results

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.

Conclusion

These data suggest that p53 down-regulates HPV 16 DNA replication via the E2 protein.