Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1

作者：Lin, Zhenghong; Tan, Can; Qiu, Quan; Kong, Sinyi; Yang, Heeyoung; Zhao, Fang; Liu, Zhaojian; Li, Jinping; Kong, Qingfei; Gao, Beixue; Barrett, Terry; Yang, Guang-Yu; Zhang, Jianing; Fang, Deyu^*

来源：Cell Discovery, 2015, 1(1): 15028.

DOI：10.1038/celldisc.2015.28

• USP22
• CCNB1
• APC8
• cell cycle
• tumorigenesis

The elevated level of CCNB1 indicates more aggressive cancer and poor prognosis. However, the factors that cause CCNB1 upregulation remain enigmatic. Herein, we identify USP22 as a CCNB1 interactor and discover that both USP22 and CCNB1 are dramatically elevated with a strong positive correlation in colon cancer tissues. USP22 stabilizes CCNB1 by antagonizing proteasome-mediated degradation in a cell cycle-specific manner. Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1. The ubiquitin ligase anaphase-promoting complex (APC/C) targets USP22 for degradation by using the substrate adapter CDC20 during cell exit from M phase, presumably allowing CCNB1 degradation. Finally, we discover that USP22 knockdown leads to slower cell growth and reduced tumor size. Our study demonstrates that USP22 is a CCNB1 deubiquitinase, suggesting that targeting USP22 might be an effective approach to treat cancers with elevated CCNB1 expression.

• 出版日期2015
• 单位西北大学; 重庆大学; 大连理工大学