Human papillomavirus type 16 E7 oncoprotein inhibits the anaphase promoting complex/cyclosome activity by dysregulating EMI1 expression in mitosis

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• 作者：Yueyang Yu ; Karl Munger
• 关键词：Human papillomaviruses ; E7 oncoprotein ; Mitosis ; Anaphase Promoting Complex/Cyclosome (APC/C) ; EMI1 ; Genomic instability ; Cervical cancer
• 刊名：Virology
• 出版年：2013
• 出版时间：November, 2013
• 年：2013
• 卷：446
• 期：1-2
• 页码：251-259
• 全文大小：1834 K

文摘

The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase complex that orchestrates mitotic progression by targeting key mitotic regulators for proteasomal degradation. APC/C dysfunction is a frequent event during cancer development and can give rise to genomic instability. Here we report that the HPV16 E7 oncoprotein interferes with the degradation of APC/C substrates and that the APC/C inhibitor, EMI1, is expressed at higher levels in HPV16 E7-expressing mitotic cells. HPV16 E7 expression causes increased EMI1 mRNA expression and also inhibits EMI1 degradation. The resulting abnormally high EMI1 levels in HPV16 E7-expressing mitotic cells may inhibit degradation of APC/C substrates and cause the prometaphase delay that we have previously observed in such cells.