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

Title
Genome-scale screening of deubiquitinase subfamily identifies USP3 as a stabilizer of Cdc25A regulating cell cycle in cancer
Authors
Das, SoumyadipChandrasekaran, Arun PandianSuresh, BharathiHaq, SabaKang, Jae-HyeokLee, Su-JaeKim, JaewonKim, JaesangLee, SanghyukKim, Hyongbum HenryKim, Kye-SeongRamakrishna, Suresh
Ewha Authors
이상혁김재상
SCOPUS Author ID
이상혁scopus; 김재상scopus
Issue Date
2020
Journal Title
CELL DEATH AND DIFFERENTIATION
ISSN
1350-9047JCR Link

1476-5403JCR Link
Citation
CELL DEATH AND DIFFERENTIATION vol. 27, no. 11, pp. 3004 - 3020
Publisher
SPRINGERNATURE
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
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.
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DOI
10.1038/s41418-020-0557-5
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자연과학대학 > 생명과학전공 > Journal papers
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