Genome-scale screening of deubiquitinase subfamily identifies USP3 as a stabilizer of Cdc25A regulating cell cycle in cancer
- 주제(기타) Biochemistry & Molecular Biology
- 주제(기타) Cell Biology
- 설명문(일반) [Das, Soumyadip; Chandrasekaran, Arun Pandian; Kim, Kye-Seong; Ramakrishna, Suresh] Hanyang Univ, Grad Sch Biomed Sci & Engn, Seoul, South Korea; [Suresh, Bharathi; Kim, Hyongbum Henry] Yonsei Univ, Dept Pharmacol, Coll Med, Seoul, South Korea; [Haq, Saba; Kang, Jae-Hyeok; Lee, Su-Jae] Hanyang Univ, Coll Nat Sci, Dept Life Sci, Seoul, South Korea; [Kim, Jaewon; Lee, Sanghyuk] Ewha Womans Univ, Dept Bioinformat Sci, Seoul, South Korea; [Kim, Jaesang; Lee, Sanghyuk] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea; [Kim, Hyongbum Henry] Yonsei Univ, Brain Korea 21 Plus Project Med Sci, Coll Med, Seoul, South Korea; [Kim, Hyongbum Henry] Yonsei Univ, Severance Biomed Sci Inst, Coll Med, Seoul, South Korea; [Kim, Hyongbum Henry] Inst Basic Sci IBS, Ctr Nanomed, Seoul, South Korea; [Kim, Hyongbum Henry] Yonsei Univ, Yonsei IBS Inst, Seoul, South Korea; [Kim, Kye-Seong; Ramakrishna, Suresh] Hanyang Univ, Coll Med, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, Bronze
- 발행기관 SPRINGERNATURE
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000174945
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/s41418-020-0557-5
- PubMed https://pubmed.ncbi.nlm.nih.gov/32415280
초록/요약
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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