title: Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1.
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.
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Can
authors.initials: C
authors.lastname: Tan
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Quan
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Sinyi
authors.initials: S
authors.lastname: Kong
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Heeyoung
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Jinping
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Qingfei
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Beixue
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Barrett
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Yang
authors.affiliation: School of Life Science and Medicine, Dalian University of Technology, Panjin, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; School of Life Science and Medicine, Dalian University of Technology, Panjin, China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
keywords: APC8; CCNB1; USP22; cell cycle; tumorigenesis