A role for ATR in the DNA damage-induced phosphorylation of p53
A role for ATR in the DNA damage-induced phosphorylation of p53
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DOI：
10.1101/gad.13.2.152
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发表时间：
1999-01-15
影响因子：
10.5
通讯作者：
Abraham, RT
中科院分区：
文献类型：
--
作者：
Tibbetts, RS;Brumbaugh, KM;Abraham, RT
Ser-15磷酸化可能是细胞应激过程中p53上调和功能激活的关键事件。在这份报告中，我们提供的证据表明，ATM-Rad 3相关蛋白ATR调节DNA损伤细胞中Ser-15的磷酸化。在人成纤维细胞中过表达无催化活性的ATR（ATR（ki））抑制Ser-15磷酸化对γ-照射和UV光的响应。在γ射线照射的细胞中，ATR（ki）的表达选择性地干扰晚期Ser-15磷酸化，而ATR（ki）以时间不依赖的方式阻断UV诱导的Ser-15磷酸化。ATR在体外磷酸化p53的Ser-15和Ser-37，表明p53是ATR在DNA损伤细胞中磷酸化的靶点。
Phosphorylation at Ser-15 may be a critical event in the up-regulation and functional activation of p53 during cellular stress. In this report we provide evidence that the ATM-Rad3-related protein ATR regulates phosphorylation of Ser-15 in DNA-damaged cells. Overexpression of catalytically inactive ATR (ATR(ki)) in human fibroblasts inhibited Ser-15 phosphorylation in response to gamma-irradiation and UV light. In gamma-irradiated cells, ATR(ki) expression selectively interfered with late-phase Ser-15 phosphorylation, whereas ATR(ki) blocked UV-induced Ser-15 phosphorylation in a time-independent manner. ATR phosphorylated p53 at Ser-15 and Ser-37 in vitro, suggesting that p53 is a target for phosphorylation by ATR in DNA-damaged cells.