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Genome-scale screening of deubiquitinase subfamily identifies USP3 as a stabilizer of Cdc25A regulating cell cycle in cancer

Authors
 Soumyadip Das  ;  Arun Pandian Chandrasekaran  ;  Bharathi Suresh  ;  Saba Haq  ;  Jae-Hyeok Kang  ;  Su-Jae Lee  ;  Jaewon Kim  ;  Jaesang Kim  ;  Sanghyuk Lee  ;  Hyongbum Henry Kim  ;  Kye-Seong Kim  ;  Suresh Ramakrishna 
Citation
 CELL DEATH AND DIFFERENTIATION, Vol.27(11) : 3004-3020, 2020-11 
Journal Title
 CELL DEATH AND DIFFERENTIATION 
ISSN
 1350-9047 
Issue Date
2020-11
Abstract
Conventional screening methods for deubiquitinating enzymes (DUBs) have important limitations. A loss-of-function study based on the knockout of DUB genes in mammalian cells can provide an excellent model for exploring DUB function. Here, we used CRISPR-Cas9 to perform genome-scale knockout of the entire set of genes encoding ubiquitin-specific proteases (USPs), a DUB subfamily, and then systematically screened for DUBs that stabilize the Cdc25A oncoprotein. USP3 was identified as a deubiquitinase of Cdc25A. USP3 depletion reduces the Cdc25A protein level, resulting in a significant delay in cell-cycle progression, and reduces the growth of cervical tumor xenografts in nude mice. Clinically, USP3 expression is positively correlated with Cdc25A protein expression and the poorest survival in breast cancer. We envision that our DUB knockout library kit will facilitate genome-scale screening of functional DUBs for target proteins of interest in a wide range of biomedical fields.
Full Text
https://www.nature.com/articles/s41418-020-0557-5
DOI
10.1038/s41418-020-0557-5
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyongbum(김형범) ORCID logo https://orcid.org/0000-0002-4693-738X
Suresh, Bharathi(호사발레랑가파바라티)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/181516
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