A novel ATM-Dependent pathway regulates protein phosphatase 1 in response to DNA damage
A novel ATM-Dependent pathway regulates protein phosphatase 1 in response to DNA damage
复制标题
一种新的 ATM 依赖性途径调节蛋白磷酸酶 1 以响应 DNA 损伤
DOI：
10.1128/mcb.01711-07
复制
发表时间：
2008-04-01
影响因子：
5.3
通讯作者：
Xu, Bo
中科院分区：
文献类型：
--
作者：
Tang, Xi;Hui, Zhou-guang;Xu, Bo
蛋白磷酸酶1（PP 1）是一种重要的蛋白磷酸酶，对多种细胞反应很重要，在电离辐射（IR）诱导的DNA损伤中被激活。在这里，我们报告说，IR诱导PP 1从其调节亚基抑制剂-2（I-2）的快速解离，该过程需要共济失调血管扩张突变（ATM），一种蛋白激酶的核心DNA损伤反应。作为对IR的响应，ATM使丝氨酸43上的I-2磷酸化，导致PPI-I-2复合物的解离和PP 1的活化。此外，ATM介导的1-2磷酸化导致Aurora-B激酶的抑制、组蛋白H3丝氨酸10磷酸化的下调和G（2）/M检查点的激活。总的来说，这些研究的结果证明了一种新的途径，该途径将ATM，PP 1和I-2联系在细胞对DNA损伤的反应中。
Protein phosphatase 1 (PP1), a major protein phosphatase important for a variety of cellular responses, is activated in response to ionizing irradiation (IR)-induced DNA damage. Here, we report that IR induces the rapid dissociation of PP1 from its regulatory subunit inhibitor-2 (I-2) and that the process requires ataxiatelangiectasia mutated (ATM), a protein kinase central to DNA damage responses. In response to IR, ATM phosphorylates I-2 on serine 43, leading to the dissociation of the PPI-I-2 complex and the activation of PP1. Furthermore, ATM-mediated 1-2 phosphorylation results in the inhibition of the Aurora-B kinase, the downregulation of histone H3 serine 10 phosphoryllation, and the activation of the G(2)/M checkpoint. Collectively, the results of these studies demonstrate a novel pathway that links ATM, PP1, and I-2 in the cellular response to DNA damage.