The DNA-dependent protein kinase is inactivated by autophosphorylation of the catalytic subunit
The DNA-dependent protein kinase is inactivated by autophosphorylation of the catalytic subunit
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DOI：
10.1074/jbc.271.15.8936
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发表时间：
1996-04-12
影响因子：
4.8
通讯作者：
LeesMiller, SP
中科院分区：
文献类型：
--
作者：
Chan, DW;LeesMiller, SP
DNA依赖性蛋白激酶（DNA-PK）需要双链DNA结构中的活性自由末端或其他不连续性。在体外，DNA-PK磷酸化多种转录因子和其他DNA结合蛋白，并被认为在DNA损伤识别或修复和/或转录中发挥作用。在这里，我们表明，在体外DNA-PK经历的所有三个蛋白亚基（DNA-PKcs，Ku p70和Ku p80）的自磷酸化和磷酸化与失活的丝氨酸/苏氨酸激酶活性的DNA-PK显着，活性恢复通过添加纯化的天然DNA-PKcs，但不是Ku，这表明失活是由于DNA-PKcs的自磷酸化。我们的数据还表明，自磷酸化导致DNA-PKcs从Ku-DNA复合物中解离。我们认为，自磷酸化是调节DNA-PK活性的重要机制。
The DNA-dependent protein kinase (DNA-PK) requires for activity free ends or other discontinuities in the structure of double strand DNA In vitro, DNA-PK phosphorylates several transcription factors and other DNA-binding proteins and is thought to function in DNA damage recognition or repair and/or transcription. Here we show that in vitro DNA-PK undergoes autophosphorylation of all three protein subunits (DNA-PKcs, Ku p70 and Ku p80) and that phosphorylation correlates with inactivation of the serine/threonine kinase activity of DNA-PK Significantly, activity is restored by the addition of purified native DNA-PKcs but not Ku, suggesting that inactivation is due to autophosphorylation of DNA-PKcs. Our data also suggest that autophosphorylation results in dissociation of DNA-PKcs from the Ku-DNA complex. We suggest that autophosphorylation is an important mechanism for the regulation of DNA-PK activity.