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HAUSP stabilizes Cdc25A and protects cervical cancer cells from DNA damage response

Title
HAUSP stabilizes Cdc25A and protects cervical cancer cells from DNA damage response
Author
김계성
Keywords
Drug resistance; Etoposide; Knockout cells; USP7; Ultraviolet rays
Issue Date
2020-08
Publisher
ELSEVIER
Citation
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1867, no. 12, article no. 118835
Abstract
Resistance to DNA-damaging agents is one of the main reasons for the low survival of cervical cancer patients. Previous reports have suggested that the Cdc25A oncoprotein significantly affects the level of susceptibility to DNA-damaging agents, but the molecular mechanism remains unclear. In this study, we used Western blot and flow cytometry analyses to demonstrate that the deubiquitinating enzyme HAUSP stabilizes Cdc25A protein level. Furthermore, in a co-immunoprecipitation assay, we found that HAUSP interacts with and deubiquitinates Cdc25A both exogenously and endogenously. HAUSP extends the half-life of the Cdc25A protein by circumventing turnover. HAUSP knockout in HeLa cells using the CRISPR/Cas9 system caused a significant delay in Cdc25A-mediated cell cycle progression, cell migration, and colony formation and attenuated tumor progression in a mouse xenograft model. Furthermore, HAUSP-mediated stabilization of the Cdc25A protein produced enhanced resistance to DNA-damaging agents. Overall, our study suggests that targeting Cdc25A and HAUSP could be a promising combinatorial approach to halt progression and minimize antineoplastic resistance in cervical cancer.
URI
https://www.sciencedirect.com/science/article/pii/S0167488920301932?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/169901
ISSN
0167-4889; 1879-2596
DOI
10.1016/j.bbamcr.2020.118835
Appears in Collections:
GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > BIOMEDICAL SCIENCE(의생명과학과) > Articles
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