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P53 suppresses SENP3 phosphorylation to mediate G2 checkpoint.
Cell Discovery ( IF 33.5 ) Pub Date : 2020-04-21 , DOI: 10.1038/s41421-020-0154-2
Yang Wang 1, 2, 3 , Jing Tian 1, 2, 3 , Chao Huang 4 , Jiao Ma 1, 2, 3 , Gaolei Hu 1, 2, 3 , Yalan Chen 1, 2, 3 , Tianshi Wang 1, 2, 3 , Rong Cai 1, 2, 3 , Yong Zuo 1, 2, 3 , Hongsheng Tan 5 , Qiuju Fan 1, 2, 3 , Baijun Dong 1, 3 , Wei Xue 1, 3 , Jing Yi 1, 2, 3 , Guoqiang Chen 2 , Jun Tu 1, 2, 3 , Jinke Cheng 1, 2, 3
Affiliation  

In response to DNA damage, p53-mediated signaling is regulated by protein phosphorylation and ubiquitination to precisely control G2 checkpoint. Here we demonstrated that protein SUMOylation also engaged in regulation of p53-mediated G2 checkpoint. We found that G2 DNA damage suppressed SENP3 phosphorylation at G2/M phases in p53-dependent manner. We further found that the suppression of SENP3 phosphorylation was crucial for efficient DNA damage/p53-induced G2 checkpoint and G2 arrest. Mechanistically, we identified Cdh1, a subunit of APC/C complex, was a SUMOylated protein at G2/M phase. SENP3 could de-SUMOylate Cdh1. DNA damage/p53-induced suppression of SENP3 phosphorylation activated SENP3 de-SUMOylation of Cdh. De-SUMOylation promoted Cdh1 de-phosphorylation by phosphatase Cdc14B, and then activated APC/CCdh1 E3 ligase activity to ubiquitate and degrade Polo-like kinase 1 (Plk1) in process of G2 checkpoint. These data reveal that p53-mediated inhibition of SENP3 phosphorylation regulates the activation of Cdc14b-APC/CCdh1-Plk1 axis to control DNA damage-induced G2 checkpoint.

中文翻译:

P53 抑制 SENP3 磷酸化以介导 G2 检查点。

为了响应 DNA 损伤,p53 介导的信号传导受到蛋白质磷酸化和泛素化的调节,以精确控制 G2 检查点。在这里,我们证明蛋白质 SUMO 化也参与 p53 介导的 G2 检查点的调节。我们发现 G2 DNA 损伤以 p53 依赖性方式抑制 G2/M 期 SENP3 磷酸化。我们进一步发现 SENP3 磷酸化的抑制对于有效的 DNA 损伤/p53 诱导的 G2 检查点和 G2 停滞至关重要。从机制上讲,我们确定 APC/C 复合物的一个亚基 Cdh1 是 G2/M 期的 SUMO 化蛋白。SENP3 可以去 SUMOylate Cdh1。DNA 损伤/p53 诱导的 SENP3 磷酸化抑制激活了 Cdh 的 SENP3 去 SUMO 化。去SUMO化作用通过磷酸酶Cdc14B促进Cdh1去磷酸化,然后激活APC/CCdh1 E3连接酶活性,在G2检查点过程中泛素化并降解Polo样激酶1(Plk1)。这些数据表明,p53 介导的 SENP3 磷酸化抑制调节 Cdc14b-APC/CCdh1-Plk1 轴的激活,从而控制 DNA 损伤诱导的 G2 检查点。
更新日期:2020-04-24
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