Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis

Autor: Byung Ho Rhie, Soumyadip Das, Apoorvi Tyagi, Kye Seong Kim, Arun Pandian Chandrasekaran, Suresh Ramakrishna, Seung Jun Oh, Neha Sarodaya, Na Re Ko, Bharathi Suresh, Sang Hyeon Woo
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Carcinogenesis
Mice
SCID
medicine.disease_cause
tumor model
HeLa
Mice
Biology (General)
Spectroscopy
Gene knockdown
biology
Chemistry
apoptosis
General Medicine
Cell cycle
Computer Science Applications
Cell biology
Gene Expression Regulation
Neoplastic
Cell Transformation
Neoplastic
Gene Knockdown Techniques
Heterografts
cell cycle
Ubiquitin-Specific Proteases
CDC25A
proteolysis
Cell Survival
QH301-705.5
Mice
Nude
ubiquitination
Article
Catalysis
Inorganic Chemistry
medicine
Animals
Humans
cdc25 Phosphatases
Physical and Theoretical Chemistry
Molecular Biology
QD1-999
Cell Proliferation
Ubiquitin
Cell growth
oncogenic transformation
Organic Chemistry
Cell Cycle Checkpoints
Oncogenes
biology.organism_classification
deubiquitinase
HEK293 Cells
Apoptosis
Cancer cell
CRISPR-Cas Systems
HeLa Cells
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 11
International Journal of Molecular Sciences, Vol 22, Iss 5766, p 5766 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22115766
Popis: 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.
Databáze: OpenAIRE
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