期刊
ONCOGENE
卷 27, 期 55, 页码 7018-7030出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2008.351
关键词
HPV; E6; PDZ; cell polarity
资金
- ICGEB Fellowship Programme
- Associazione Italiana per la Ricerca sul Cancro
- Association for International Cancer Research
- YKK Scholarship Foundation
- Kanzawa Medical Research Foundation
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. The se 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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