USP11 regulates p53 stability by deubiquitinating p53
USP11 regulates p53 stability by deubiquitinating p53
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DOI：
10.1631/jzus.b1400180
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发表时间：
2014-12-01
影响因子：
5.1
通讯作者：
Wu, Chun-lin
中科院分区：
文献类型：
--
作者：
Ke, Jia-ying;Dai, Cong-jie;Wu, Chun-lin
p53 肿瘤抑制蛋白协调细胞对多种细胞应激的反应，导致 DNA 修复、细胞周期停滞或细胞凋亡。 p53 的稳定性对其肿瘤抑制功能至关重要，该功能主要通过其负调节因子鼠双分钟 2 (Mdm2) 受到泛素依赖性降解的严格控制。为了更好地了解 p53 的调控，我们使用免疫共沉淀测试了 p53 和 USP11 之间的相互作用。结果表明，USP11（一种泛素特异性蛋白酶）与 p53 形成特异性复合物，并通过去泛素化 p53 来稳定 p53。此外，USP11 的下调显着减弱了 DNA 损伤应激反应中 p53 的诱导。这些发现表明，USP11 是 p53 的一种新型调节因子，它是 p53 响应 DNA 损伤而激活所必需的。
The p53 tumor suppressor protein coordinates the cellular responses to a broad range of cellular stresses, leading to DNA repair, cell cycle arrest or apoptosis. The stability of p53 is essential for its tumor suppressor function, which is tightly controlled by ubiquitin-dependent degradation primarily through its negative regulator murine double minute 2 (Mdm2). To better understand the regulation of p53, we tested the interaction between p53 and USP11 using co-immunoprecipitation. The results show that USP11, an ubiquitin-specific protease, forms specific complexes with p53 and stabilizes p53 by deubiquitinating it. Moreover, down-regulation of USP11 dramatically attenuated p53 induction in response to DNA damage stress. These findings reveal that USP11 is a novel regulator of p53, which is required for p53 activation in response to DNA damage.