S-Space College of Medicine/School of Medicine (의과대학/대학원) Pathology (병리학전공) Journal Papers (저널논문_병리학전공)
Human papillomavirus type 16 E5 protein inhibits hydrogen peroxide-induced apoptosis by stimulating ubiquitin-proteasome-mediated degradation of Bax in human cervical cancer cells
- Oh, Jung-Min; Kim, Su-Hyeong; Cho, Eun-Ah; Song, Yong-Sang; Juhnn, Yong-Sung; Kim, Woo-Ho
- Issue Date
- OXFORD UNIV PRESS
- CARCINOGENESIS; Vol.31 3; 402-410
- 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 (PGE(2)) receptor antagonists and cyclic adenosine monophosphate-dependent protein kinase (PKA) inhibitor. Treatment with PGE(2) 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, PGE(2) and PKA. This finding suggests the possibility that HPV 16 E5 protein contributes to cervical carcinogenesis by inhibiting apoptosis of transformed cervical epithelial cells.
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