Banin S, Moyal L, Shieh S, Taya Y, Anderson C W, Chessa L, Smorodinsky N I, Prives C, Reiss Y, Shiloh Y, Ziv Y
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.
Science. 1998 Sep 11;281(5383):1674-7. doi: 10.1126/science.281.5383.1674.
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.
由负责人类遗传性共济失调毛细血管扩张症（A-T）的基因编码的ATM蛋白，调节细胞对DNA断裂的多种反应。ATM与几种蛋白质共享一个磷酸肌醇3激酶相关结构域，其中一些是蛋白激酶。一种对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。体外底物包括翻译抑制因子PHAS-I和p53蛋白。ATM在体外将p53的单个残基丝氨酸-15磷酸化，该残基在体内因DNA损伤而被磷酸化。在用放射模拟药物处理细胞后的几分钟内，这种活性显著增强；ATM的总量保持不变。ATM蛋白激酶活性的增强可能会激活各种损伤诱导的反应。
