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Human papillomaviruses, cervical cancer and cell polarity

Oncogene volume 27, pages 7018–7030 (2008)Cite this article

Abstract

Human papillomaviruses (HPVs) are the causative agents of a number of human cancers, of which cervical cancer is the most important. This occurs following persistent infection with a limited number of viral subtypes and is characterized by continued expression of the viral E6 and E7 oncoproteins. A unique characteristic of the cancer-causing HPV types is the presence of a PDZ recognition motif on the carboxy terminus of the E6 oncoprotein. Through this motif, E6 directs the proteasome-mediated degradation of cellular proteins involved in the regulation of cell polarity and in cell proliferation control. These include components of the Scrib and Par polarity complexes, as well as a number of other PDZ domain-containing substrates. Thus, PVs are now providing novel insights into the functioning of many of these cellular proteins, and into which of these functions, in particular, are relevant for maintaining normal cellular homeostasis. In this review, we discuss the biological consequences of papillomaviral targeting of these cell polarity regulators, both with respect to the viral life cycle and, most importantly, to the development of HPV-induced malignancy.

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Acknowledgements

We gratefully acknowledge research support provided by the ICGEB Fellowship Programme, the Associazione Italiana per la Ricerca sul Cancro and the Association for International Cancer Research. K Nagasaka is supported by the YKK Scholarship Foundation and the Kanzawa Medical Research Foundation.

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  1. International Centre for Genetic Engineering and Biotechnology, Trieste, Italy

    M Thomas, N Narayan, D Pim, V Tomaić, P Massimi, K Nagasaka, C Kranjec, N Gammoh & L Banks

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  1. M Thomas
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  2. N Narayan
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  3. D Pim
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  4. V Tomaić
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  5. P Massimi
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  6. K Nagasaka
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  8. N Gammoh
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  9. L Banks
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Correspondence to L Banks.

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Thomas, M., Narayan, N., Pim, D. et al. Human papillomaviruses, cervical cancer and cell polarity. Oncogene 27, 7018–7030 (2008). https://doi.org/10.1038/onc.2008.351

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