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Ubiquitin-independent degradation of p53 mediated by high-risk human papillomavirus protein E6

Oncogene volume 26, pages 4059–4070 (2007)Cite this article

Abstract

In vitro, high-risk human papillomavirus E6 proteins have been shown, in conjunction with E6-associated protein (E6AP), to mediate ubiquitination of p53 and its degradation by the 26S proteasome by a pathway that is thought to be analogous to Mdm2-mediated p53 degradation. However, differences in the requirements of E6/E6AP and Mdm2 to promote the degradation of p53, both in vivo and in vitro, suggest that these two E3 ligases may promote p53 degradation by distinct pathways. Using tools that disrupt ubiquitination and degradation, clear differences between E6- and Mdm2-mediated p53 degradation are presented. The consistent failure to fully protect p53 protein from E6-mediated degradation by disrupting the ubiquitin-degradation pathway provides the first evidence of an E6-dependent, ubiquitin-independent, p53 degradation pathway in vivo.

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Acknowledgements

This work was supported by Cancer Research UK and by the generosity of Reverend and Mrs Cameron through the Kitty Cameron Fund. We thank D Coomber for help with the manuscript preparation and M Scheffner for advice and reagents at the project outset.

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  1. L F Stevenson

    Present address: Clinical Sciences and Technology, BiogenIdec, 14 Cambridge Center, Cambridge, MA, 02142, USA

Authors and Affiliations

  1. Department of Cell Cycle Control, Institute of Molecular and Cell Biology, Proteos, Singapore

    S Camus, S Menéndez, C F Cheok & D P Lane

  2. Department of Surgery and Molecular Oncology, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK

    L F Stevenson & S Laín

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Correspondence to S Camus.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Camus, S., Menéndez, S., Cheok, C. et al. Ubiquitin-independent degradation of p53 mediated by high-risk human papillomavirus protein E6. Oncogene 26, 4059–4070 (2007). https://doi.org/10.1038/sj.onc.1210188

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