Activation of the ATM kinase by ionizing radiation and phosphorylation of p53
Activation of the ATM kinase by ionizing radiation and phosphorylation of p53
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DOI：
10.1126/science.281.5383.1677
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发表时间：
1998-09-11
期刊：
影响因子：
56.9
通讯作者：
Siliciano, JD
中科院分区：
文献类型：
--
作者：
Canman, CE;Lim, DS;Siliciano, JD
P53肿瘤抑制蛋白在丝氨酸-15上被激活和磷酸化，以响应各种DNA损伤剂。在共济失调毛细血管扩张症(ATM)中突变的基因产物在电离辐射启动的信号转导通路中作用于P53的上游。免疫沉淀的ATM具有固有的蛋白激酶活性，并以锰依赖的方式磷酸化丝氨酸-15上的P53。电离辐射，而不是紫外线辐射，迅速增强了内源性ATM的这种P53导向的激酶活性。这些观察结果，以及电离辐射导致共济失调毛细血管扩张细胞中丝氨酸-15上P53的磷酸化减少的事实，表明ATM是体内磷酸化P53的蛋白激酶。
The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. Immunoprecipitated ATM had intrinsic protein kinase activity and phosphorylated p53 on serine-15 in a manganese-dependent manner. Ionizing radiation, but not ultraviolet radiation, rapidly enhanced this p53-directed kinase activity of endogenous ATM. These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo.