Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1

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

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

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.

Original languageEnglish
Article number15028
JournalCell Discovery
Volume1
DOIs
StatePublished - Oct 13 2015

Keywords

  • APC8
  • CCNB1
  • USP22
  • cell cycle
  • tumorigenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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