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The SUMO‐specific protease SENP1 deSUMOylates p53 and regulates its activity
Author(s) -
Chauhan Krishna M.,
Chen Yingxiao,
Chen Yiyi,
Liu Andrew T.,
Sun XiaoXin,
Dai MuShui
Publication year - 2021
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29838
Subject(s) - sumo protein , transactivation , protease , gene knockdown , cancer cell , microbiology and biotechnology , suppressor , biology , p53 protein , enzyme , dna damage , chemistry , biochemistry , dna , gene expression , cancer , gene , ubiquitin , genetics
The stability and activity of the p53 tumor suppressor protein are tightly regulated by various posttranslational modifications, including SUMOylation. p53 can be modified by both SUMO1 and SUMO2, although how SUMOylation regulates p53 activity is still obscure. Whether p53 activity is directly regulated by deSUMOylation is also unclear. Here, we show that SENP1, a SUMO‐specific protease implicated in pro‐oncogenic roles, is a p53 deSUMOylating enzyme. SENP1 interacts with p53 and deSUMOylates p53 in cells and in vitro. Knockdown of SENP1 markedly induced p53 transactivation activity. We further show that SENP1 depletion synergizes with DNA damage‐inducing agent etoposide to induce p53 activation and the expression of p21, leading to synergistic growth inhibition of cancer cells. Our results reveal that SENP1 is a critical p53 deSUMOylating enzyme and a promising therapeutic target in wild‐type p53 containing cancer cells.