Enhanced phosphorylation of p53 by ATN in response to DNA damage
Enhanced phosphorylation of p53 by ATN in response to DNA damage
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DOI：
10.1126/science.281.5383.1674
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发表时间：
1998-09-11
期刊：
影响因子：
56.9
通讯作者：
Ziv, Y
中科院分区：
文献类型：
--
作者：
Banin, S;Moyal, L;Ziv, Y
ATM 蛋白由导致人类遗传性疾病毛细血管扩张性共济失调 (A-T) 的基因编码，可调节多种细胞对 DNA 断裂的反应。 ATM 与多种蛋白质（其中一些是蛋白激酶）共享一个磷酸肌醇 3 激酶相关结构域。渥曼青霉素敏感的蛋白激酶活性与内源性或重组ATM相关，并被ATM结构突变所消除。体外底物包括翻译阻遏蛋白 PHAS-I 和 p53 蛋白。 ATM 在体外将 p53 的单个残基丝氨酸 15 磷酸化，该残基在体内响应 DNA 损伤而被磷酸化。用拟放射药物处理细胞后几分钟内，这种活性就显着增强； ATM总量保持不变。 ATM 蛋白激酶活性的增强可能会激活各种损伤诱导的反应。
The ATM protein, encoded by the gene responsible for the human genetic disorder ataxia telangiectasia (A-T), regulates several cellular responses to DNA breaks. ATM shares a phosphoinositide 3-kinase-related domain with several proteins, some of them protein kinases. A wortmannin-sensitive protein kinase activity was associated with endogenous or recombinant ATM and was abolished by structural ATM mutations. In vitro substrates included the translation repressor PHAS-I and the p53 protein. ATM phosphorylated p53 in vitro on a single residue, serine-15, which is phosphorylated in vivo in response to DNA damage. This activity was markedly enhanced within minutes after treatment of cells with a radiomimetic drug; the total amount of ATM remained unchanged. Various damage-induced responses may be activated by enhancement of the protein kinase activity of ATM.