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Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis

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Abstract
Cell division cycle 25A (Cdc25A) is a dual-specificity phosphatase that is overexpressed in several cancer cells and promotes tumorigenesis. In normal cells, Cdc25A expression is regulated tightly, but the changes in expression patterns in cancer cells that lead to tumorigenesis are unknown. In this study, we showed that ubiquitin-specific protease 29 (USP29) stabilized Cdc25A protein expression in cancer cell lines by protecting it from ubiquitin-mediated proteasomal degradation. The presence of USP29 effectively blocked polyubiquitination of Cdc25A and extended its half-life. CRISPR-Cas9-mediated knockdown of USP29 in HeLa cells resulted in cell cycle arrest at the G0/G1 phase. We also showed that USP29 knockdown hampered Cdc25A-mediated cell proliferation, migration, and invasion of cancer cells in vitro. Moreover, NSG nude mice transplanted with USP29-depleted cells significantly reduced the size of the tumors, whereas the reconstitution of Cdc25A in USP29-depleted cells significantly increased the tumor size. Altogether, our results implied that USP29 promoted cell cycle progression and oncogenic transformation by regulating protein turnover of Cdc25A.
Author(s)
오승준Apoorvi TyagiArun Pandian ChandrasekaranBharathi SureshByung Ho RhieKye-Seong KimNa Re KoNeha SarodayaSang Hyeon WooSoumyadip DasSuresh Ramakrishna
Issued Date
2021
Type
Article
Keyword
apoptosiscell cycledeubiquitinaseoncogenic transformationproteolysistumor modelubiquitination
DOI
10.3390/ijms22115766
URI
https://oak.ulsan.ac.kr/handle/2021.oak/9572
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_557aa77f2d8c428cae759d075a854336&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Ubiquitin-Specific%20Protease%2029%20Regulates%20Cdc25A-Mediated%20Tumorigenesis&offset=0&pcAvailability=true
Publisher
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Location
스위스
Language
영어
ISSN
1422-0067
Citation Volume
22
Citation Number
11
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Natural Science > Biological Sciences
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