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.

中文翻译：

---

SUMO 特异性蛋白酶 SENP1 deSUMOylate p53 并调节其活性。

p53 肿瘤抑制蛋白的稳定性和活性受到各种翻译后修饰的严格调节，包括 SUMO 化。p53 可以被 SUMO1 和 SUMO2 修饰，尽管 SUMOylation 如何调节 p53 活性仍不清楚。p53 活性是否直接受 deSUMOylation 调节也不清楚。在这里，我们表明 SENP1 是一种与促癌作用有关的 SUMO 特异性蛋白酶，是一种 p53 去SUMO化酶。SENP1 与 p53 相互作用并在细胞中和体外使 p53 脱硫。敲除 SENP1 显着诱导 p53 反式激活活性。我们进一步表明，SENP1 耗竭与 DNA 损伤诱导剂依托泊苷协同诱导 p53 活化和 p21 表达，从而协同抑制癌细胞生长。