小鼠p53蛋白第18位丝氨酸的磷酸化调节p53对DNA损伤的反应。
Phosphorylation of murine p53 at ser-18 regulates the p53 responses to DNA damage.
作者信息
Chao C, Saito S, Anderson C W, Appella E, Xu Y
机构信息
Division of Biology and Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.
出版信息
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):11936-41. doi: 10.1073/pnas.220252297.
Ser-15 of human p53 (corresponding to Ser-18 of mouse p53) is phosphorylated by ataxia-telangiectasia mutated (ATM) family kinases in response to ionizing radiation (IR) and UV light. To determine the effects of phosphorylation of endogenous murine p53 at Ser-18 on biological responses to DNA damage, we introduced a missense mutation (Ser-18 to Ala) by homologous recombination into both alleles of the endogenous p53 gene in mouse embryonic stem (ES) cells. Our analyses showed that phosphorylation of murine p53 at Ser-18 in response to IR or UV radiation was required for a full p53-mediated response to these DNA damage-inducing agents. In contrast, phosphorylation of p53 at Ser-18 was not required for ATM-dependent cellular resistance after exposure to IR. Additionally, efficient acetylation of the C terminus of p53 in response to DNA damage did not require phosphorylation of murine p53 at Ser-18.
人类p53的丝氨酸15位点（对应小鼠p53的丝氨酸18位点）在受到电离辐射（IR）和紫外线照射时会被共济失调毛细血管扩张症突变（ATM）家族激酶磷酸化。为了确定内源性小鼠p53丝氨酸18位点磷酸化对DNA损伤生物学反应的影响，我们通过同源重组将一个错义突变（丝氨酸18突变为丙氨酸）引入小鼠胚胎干细胞（ES细胞）内源性p53基因的两个等位基因中。我们的分析表明，对这些DNA损伤诱导剂的完全p53介导反应需要小鼠p53在丝氨酸18位点对IR或紫外线辐射做出磷酸化反应。相比之下，暴露于IR后，ATM依赖性细胞抗性并不需要p53在丝氨酸18位点的磷酸化。此外，p53 C末端对DNA损伤做出有效乙酰化反应并不需要小鼠p53在丝氨酸18位点的磷酸化。
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