Role of HPV E6 proteins in preventing UVB-induced release of pro-apoptotic factors from the mitochondria.

Leverrier, Sabrina and Bergamaschi, Daniele and Ghali, Lucy and Ola, Ayodele and Warnes, Gary and Akgul, Baki and Blight, Ken and Garcia-Escudero, Ramon and Penna, Aubin and Eddaoudi, Ayad and Storey, Alan (2007) Role of HPV E6 proteins in preventing UVB-induced release of pro-apoptotic factors from the mitochondria. Apoptosis: an international journal on programmed cell death, 12 (3). pp. 549-560. ISSN 1360-8185

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Apoptotic elimination of UV-damaged cells from the epidermis is an important step in preventing both the emergence and expansion of cells with carcinogenic potential. A pivotal event in apoptosis is the release of apoptogenic factors from the mitochondria, although the mechanisms by which the different proteins are released are not fully understood. Here we demonstrate that UV radiation induced the mitochondrial to nuclear translocation of apoptosis inducing factor (AIF) in normal skin. The human papillomavirus (HPV) E6 protein prevented release of AIF and other apoptotic factors such as cytochrome c and Omi from mitochondria of UV-damaged primary epidermal keratinocytes and preserved mitochondrial integrity. shRNA silencing of Bak, a target for E6-mediated proteolysis, demonstrated the requirement of Bak for UV-induced AIF release and mitochondrial fragmentation. Furthermore, screening non-melanoma skin cancer biopsies revealed an inverse correlation between HPV status and AIF nuclear translocation. Our results indicate that the E6 activity towards Bak is a key factor that promotes survival of HPV-infected cells that facilitates tumor development.

Item Type:Article
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PubMed PMID: 17195958.

Research Areas:A. > School of Science and Technology > Natural Sciences > Biomarkers for Cancer group
Citations on ISI Web of Science:25
ID Code:2525
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Deposited On:18 Jun 2009 13:26
Last Modified:13 Mar 2015 14:47

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