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

doi:10.1038/celldisc.2015.28

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 journal › Article › peer-review

65 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 language	English
Article number	15028
Journal	Cell Discovery
Volume	1
DOIs	https://doi.org/10.1038/celldisc.2015.28
State	Published - Oct 13 2015

Keywords

APC8
CCNB1
USP22
cell cycle
tumorigenesis

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/celldisc.2015.28

Cite this

@article{379042a8e25c4ccb9929c070ed2a54b8,

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.",

keywords = "APC8, CCNB1, USP22, cell cycle, tumorigenesis",

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

year = "2015",

month = oct,

day = "13",

doi = "10.1038/celldisc.2015.28",

language = "English",

volume = "1",

}

TY - JOUR

T1 - Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1

AU - Lin, Zhenghong

AU - Tan, Can

AU - Qiu, Quan

AU - Kong, Sinyi

AU - Yang, Heeyoung

AU - Zhao, Fang

AU - Liu, Zhaojian

AU - Li, Jinping

AU - Kong, Qingfei

AU - Gao, Beixue

AU - Barrett, Terry

AU - Yang, Guang Yu

AU - Zhang, Jianing

AU - Fang, Deyu

PY - 2015/10/13

Y1 - 2015/10/13

N2 - 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.

AB - 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.

KW - APC8

KW - CCNB1

KW - USP22

KW - cell cycle

KW - tumorigenesis

UR - http://www.scopus.com/inward/record.url?scp=84979686783&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979686783&partnerID=8YFLogxK

U2 - 10.1038/celldisc.2015.28

DO - 10.1038/celldisc.2015.28

M3 - Article

AN - SCOPUS:84979686783

SN - 2056-5968

VL - 1

JO - Cell Discovery

JF - Cell Discovery

M1 - 15028

ER -

Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this