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Journal of Virology, May 2006, p. 4580-4590, Vol. 80, No. 9
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.9.4580-4590.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

E2 Proteins from High- and Low-Risk Human Papillomavirus Types Differ in Their Ability To Bind p53 and Induce Apoptotic Cell Death

Joanna L. Parish,^1, Anna Kowalczyk,¹ Hsin-Tien Chen,¹ Geraldine E. Roeder,¹ Richard Sessions,¹ Malcolm Buckle,² and Kevin Gaston^1*

Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom,¹ Enzymologie et Cinétique Structurale, LBPA (UMR 8113 du CNRS), Ecole Normale Supérieur de Cachan, 61 Avenue du President Wilson, 94235 Cachan, France²

Received 5 August 2005/ Accepted 2 February 2006

The E2 proteins from oncogenic (high-risk) human papillomaviruses (HPVs) can induce apoptotic cell death in both HPV-transformed and non-HPV-transformed cells. Here we show that the E2 proteins from HPV type 6 (HPV6) and HPV11, two nononcogenic (low-risk) HPV types, fail to induce apoptosis. Unlike the high-risk HPV16 E2 protein, these low-risk E2 proteins fail to bind p53 and fail to induce p53-dependent transcription activation. Interestingly, neither the ability of p53 to activate transcription nor the ability of p53 to bind DNA, are required for HPV16 E2-induced apoptosis in non-HPV-transformed cells. However, mutations that reduce the binding of the HPV16 E2 protein to p53 inhibit E2-induced apoptosis in non-HPV-transformed cells. In contrast, the interaction between HPV16 E2 and p53 is not required for this E2 protein to induce apoptosis in HPV-transformed cells. Thus, our data suggest that this high-risk HPV E2 protein induces apoptosis via two pathways. One pathway involves the binding of E2 to p53 and can operate in both HPV-transformed and non-HPV-transformed cells. The second pathway requires the binding of E2 to the viral genome and can only operate in HPV-transformed cells.

Present address: University of Massachusetts Medical School, 364 Plantation Street, Worcester MA 01605.

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