Jongmans W, Artuso M, Vuillaume M, Brésil H, Jackson S P, Hall J
Unit of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, Lyon, France.
Oncogene. 1996 Sep 19;13(6):1133-8.
The DNA-dependent protein kinase (DNA-PK), whose catalytic subunit shows structural similarities to the Ataxia telangiectasia (AT) gene product (ATM), has also been implicated in the p53-mediated signal transduction pathway that activates the cellular response to DNA damage produced by ionizing radiation. DNA-PK activity however was not found to be related to the transcriptional induction of WAFl/CIP1(p2l) in AT lymphoblastoid cell lines, following treatment with ionizing radiation. Normal protein and transcription levels of Ku70 and Ku80, as well as DNA-PK activity, were found in six different AT cell lines, 1-4 h following exposure to ionizing radiation, timepoints where reduced and delayed transcriptional induction of WAF1/CIP1 (p21) was observed. WAF1/CIP1 (p21) was found to be transcriptionally induced by p53 in normal cell lines over this same time period following exposure to ionizing radiation. These results suggest that despite the findings that in vitro DNA-PK may phosphorylate p53, in vivo it would not appear to play a central role in the activation of p53 as a transcription factor nor can it substitute for the ATM gene product in the cellular response following exposure to ionizing radiation.
DNA依赖性蛋白激酶（DNA-PK），其催化亚基与共济失调毛细血管扩张症（AT）基因产物（ATM）在结构上相似，也参与了p53介导的信号转导途径，该途径可激活细胞对电离辐射产生的DNA损伤的反应。然而，在用电离辐射处理后，在AT淋巴母细胞系中未发现DNA-PK活性与WAFl/CIP1（p2l）的转录诱导有关。在六种不同的AT细胞系中，在暴露于电离辐射后1-4小时发现Ku70和Ku80的正常蛋白质和转录水平以及DNA-PK活性，在这些时间点观察到WAF1/CIP1（p21）的转录诱导减少和延迟。在正常细胞系中，在暴露于电离辐射后的同一时间段内，发现WAF1/CIP1（p21）由p53转录诱导。这些结果表明，尽管有研究发现体外DNA-PK可能使p53磷酸化，但在体内它似乎在激活作为转录因子的p53中不发挥核心作用，也不能在暴露于电离辐射后的细胞反应中替代ATM基因产物。
