Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation
Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation
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DOI：
10.1101/gad.1176004
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发表时间：
2004-02-01
影响因子：
10.5
通讯作者：
Wang, XF
中科院分区：
文献类型：
--
作者：
Ali, A;Zhang, J;Wang, XF
检查点激酶ATM主要参与细胞对DNA双链断裂的反应。然而，在遗传毒性应激过程中ATM激活的机制仅部分了解。在这里，我们报告了蛋白质丝氨酸-苏氨酸磷酸酶5（PP 5）和ATM之间的直接调节联系。PP 5以DNA损伤诱导的方式与ATM相互作用。PP 5的表达减少可减弱DNA损伤诱导的ATM活化。无催化活性的PP 5突变体的表达抑制ATM底物的磷酸化和ATM在Ser 1981上的自磷酸化，并在DNA损伤的细胞中引起S期检查点缺陷。总之，我们的研究结果表明，PP 5在DNA双链断裂的细胞中ATM的激活和检查点信号功能中起着至关重要的作用。
The checkpoint kinase ATM is centrally involved in the cellular response to DNA double-strand breaks. However, the mechanism of ATM activation during genotoxic stress is only partially understood. Here we report a direct regulatory linkage between the protein serine-threonine phosphatase 5 (PP5) and ATM. PP5 interacts with ATM in a DNA-damage-inducible manner. Reduced expression of PP5 attenuated DNA-damage-induced activation of ATM. Expression of a catalytically inactive PP5 mutant inhibited the phosphorylation of ATM substrates and the autophosphorylation of ATM on Ser 1981, and caused an S-phase checkpoint defect in DNA-damaged cells. Together our findings indicate that PP5 plays an essential role in the activation and checkpoint signaling functions of ATM in cells that have suffered DNA double-strand breaks.