DNA damage-induced apoptosis requires the DNA-dependent protein kinase, and is mediated by the latent population of p53.
DNA damage-induced apoptosis requires the DNA-dependent protein kinase, and is mediated by the latent population of p53.
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DNA 损伤诱导的细胞凋亡需要 DNA 依赖性蛋白激酶，并由 p53 的潜在群体介导。
DOI：
10.1093/emboj/cdf307
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Lee,PatrickWK
中科院分区：
文献类型：
--
作者：
Woo,RichardA;Jack,MelissaT;Xu,Yang;Burma,Sandeep;Chen,DavidJ;Lee,PatrickWK
Mouse embryo fibroblasts (MEFs) expressing the adenovirus E1A protein undergo apoptosis upon exposure to ionizing radiation. We show here that immediately following γ‐irradiation, latent p53 formed a complex with the catalytic subunit of the DNA‐dependent protein kinase (DNA‐PK CS). The complex formation was DNase sensitive, suggesting that the proteins came together on the DNA, conceivably at strand breaks. This association was accompanied by phosphorylation of pre‐existing, latent p53 at Ser18 (corresponding to Ser15 in human p53), which was not found in DNA‐PK CS−/− cells. Most significantly, DNA damage‐induced apoptosis was abolished in both DNA‐PK CS−/− and p53−/− cells. In addition, blocking synthesis of inducible p53 by cycloheximide did not abrogate apoptosis, suggesting that the latent population of p53 is sufficient for executing the apoptotic program. Finally, E1A‐expressing MEFs from a p53 ‘knock‐in’mouse where Ser18 was mutated to an alanine had an attenuated apoptotic response, indicating that phosphorylation of this site by DNA‐PK is a contributing factor for apoptosis.
