USP49 participates in the DNA damage response by forming a positive feedback loop with p53

Cell Death & Disease
Rongfu TuRun-Lei Du

Abstract

The p53 tumor suppressor is a critical factor in the DNA damage response (DDR), and regulation of p53 stability has a key role in this process. In our study, we identified USP49 as a novel deubiquitinase (DUB) for p53 from a library consisting of 80 DUBs and found that USP49 has a positive effect on p53 transcriptional activity and protein stability. Investigation of the mechanism revealed that USP49 interacts with the N terminus of p53 and suppresses several types of p53 ubiquitination. Furthermore, USP49 rendered HCT116 cells more sensitive to etoposide (Eto)-induced DNA damage and was upregulated in response to several types of cell stress, including DNA damage. Remarkably, USP49 expression was regulated by p53 and USP49 in knockout mice, which are more susceptible to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon tumors. These findings suggest that USP49 has an important role in DDR and may act as a potential tumor suppressor by forming a positive feedback loop with p53.

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Citations

Apr 20, 2019·The Kaohsiung Journal of Medical Sciences·Wen-Ming ShenShi-Ying Zheng
Jun 19, 2020·Cancers·Ainsley Mike AntaoSuresh Ramakrishna
Jul 22, 2020·Journal of Clinical Laboratory Analysis·Xinye QianJun Zhang
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Sep 2, 2020·Journal of Experimental & Clinical Cancer Research : CR·Xiaobin GuoZhihua Liu
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Mar 24, 2020·Seminars in Cancer Biology·Thomas Bonacci, Michael J Emanuele
Jun 29, 2021·Genes & Diseases·Juan LiuZhaohui Feng

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Methods Mentioned

BETA
ubiquitination
deubiquitination
co-immunoprecipitation
pull-down
immunoprecipitation
nuclear translocation
PCR
transfections
Protein Assay
electrophoresis

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