张嘉宁

个人信息Personal Information

教授

博士生导师

硕士生导师

性别:男

毕业院校:日本京都大学

学位:博士

所在单位:化工海洋与生命学院

电子邮箱:jnzhang@dlut.edu.cn

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Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1

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论文类型:期刊论文

发表时间:2015-01-01

发表刊物:CELL DISCOVERY

收录刊物:SCIE、PubMed

卷号:1

ISSN号:2056-5968

关键字:USP22; CCNB1; APC8; cell cycle; tumorigenesis

摘要: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.