期刊
VIROLOGY
卷 400, 期 1, 页码 44-52出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2010.01.009
关键词
HPV-16; E5 oncoprotein; High-risk papillomaviruses; p27(Kip1); Cell cycle regulation; EGF-receptor
类别
资金
- CONACYT-SEP [38906-M]
- Miguel Aleman Foundation
- Cancer Research UK [12011] Funding Source: researchfish
E5 oncoprotein activity from high risk human papillomaviruses (HPVs) is associated with growth factor receptor signaling, but the function of this protein is not well understood. In this study, we investigated the role of HPV-16 E5 on the cell cycle progression during EGF-stimulation. Wild-type and NIH 3T3 cells over-expressing human EGF-receptor were transfected with HPV-16 E5 gene and the cell cycle progression was characterized. This analysis showed that the E5-expressing cells increased DNA synthesis (S-phase) by around 40%. Cell cycle protein analysis of E5-expressing cells showed a reduction in the half-life of p27(Kip1) protein as compared to control cells (18.4 vs. 12.7 h), an effect that was enhanced in EGF-stimulated cells (12.8 vs. 3.6 h). Blockage of EGF-receptor activity abrogated E5 signals as well as p27(Kip1) down-regulation. These results suggest that E5 and the EGF-receptor cooperate to enhance cell cycle entry and progression through regulating p27(Kip1) expression at procein level. (C) 2010 Elsevier Inc. All rights reserved.
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