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The role of the E6-p53 interaction in the molecular pathogenesis of HPV

Oncogene volume 18, pages 7690–7700 (1999)Cite this article

Abstract

Human papillomaviruses (HPVs) are associated with a number of clinical conditions, of which the most serious is cervical carcinoma. The E6 protein of the oncogenic, mucosal-specific HPV types has been shown to complex with p53 and, as a result, target it for rapid proteasome-mediated degradation. As a consequence, p53's growth-arrest and apoptosis-inducing activities are abrogated. Since p53 is frequently wild type in cervical cancers, unlike other cancers in which it is often mutated, the notion has arisen that E6's activity with respect to p53 is equivalent to an inactivating mutation of p53. In addition, several studies have shown that the pathways both upstream and downstream of p53 are intact in cervical cancers; this suggests the potential importance of the E6 – p53 interaction for therapeutic intervention. However, like all viral oncoproteins, E6 is a multifunctional protein and a plethora of other cellular targets has been identified. Indeed, E6's interactions with some of these additional targets appear to be equally important in the pathogenesis of HPV, and may also represent valid targets for therapeutic intervention.

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Acknowledgements

We would like to thank Christian Kühne, for his useful comments on the manuscript. We gratefully acknowledge the research support provided by the Associazione Italiana per la Ricerca sul Cancro and the European Union BioMed 2 Programme.

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    Miranda Thomas, David Pim & Lawrence Banks

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Thomas, M., Pim, D. & Banks, L. The role of the E6-p53 interaction in the molecular pathogenesis of HPV. Oncogene 18, 7690–7700 (1999). https://doi.org/10.1038/sj.onc.1202953

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