Journal Article

Human papillomavirus type 16 E5 protein inhibits hydrogen peroxide-induced apoptosis by stimulating ubiquitin–proteasome-mediated degradation of Bax in human cervical cancer cells

Jung-Min Oh, Su-Hyeong Kim, Eun-Ah Cho, Yong-Sang Song, Woo-Ho Kim and Yong-Sung Juhnn

in Carcinogenesis

Volume 31, issue 3, pages 402-410
Published in print March 2010 | ISSN: 0143-3334
Published online December 2009 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgp318
Human papillomavirus type 16 E5 protein inhibits hydrogen peroxide-induced apoptosis by stimulating ubiquitin–proteasome-mediated degradation of Bax in human cervical cancer cells

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To investigate the mechanism by which the human papillomavirus (HPV) E5 protein contributes to the carcinogenesis of uterine cervical cancer, we studied the effect of HPV E5 on apoptosis of cervical cancer cells and its underlying mechanism. Expression of HPV16 E5 protein inhibited hydrogen peroxide-induced apoptosis in C-33A cervical cancer cells. E5 decreased the expression of Bax protein, and exogenous expression of Bax abolished the anti-apoptotic effect of E5. Knockdown of E5 by small interfering RNA sensitized CaSki cervical cancer cells to hydrogen peroxide-induced apoptosis with concurrent increase in Bax expression. Transient expression of E5 significantly increased the degradation rate of Bax protein by inducing the ubiquitination. The E5-induced decrease in Bax expression was inhibited by a cyclooxygenase-2 (COX-2) inhibitor, prostaglandin E2 (PGE2) receptor antagonists and cyclic adenosine monophosphate-dependent protein kinase (PKA) inhibitor. Treatment with PGE2 decreased the expression of Bax and inhibited hydrogen peroxide-induced apoptosis of C-33A cells. We concluded that HPV16 E5 protein inhibits hydrogen peroxide-induced apoptosis of cervical cancer cells by stimulating the ubiquitin–proteasome-mediated degradation of Bax protein, and the pathway involves COX-2, PGE2 and PKA. This finding suggests the possibility that HPV 16 E5 protein contributes to cervical carcinogenesis by inhibiting apoptosis of transformed cervical epithelial cells.

Journal Article.  6349 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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