The DNA-dependent protein kinase, DNA-PK: 10 years and no ends in sight

The DNA-dependent protein kinase, DNA-PK: 10 years and no ends in sight
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DOI:
10.1139/o96-054
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发表时间:
1996-01-01
期刊:
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE
影响因子:
--
通讯作者:
LeesMiller, SP
LeesMiller, SP
中科院分区:
其他
文献类型:
--
作者:
LeesMiller, SP

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DNA依赖性蛋白质磷酸化的现象在10年前首次被描述。从那时起,DNA依赖性蛋白激酶DNA-PK已从人类细胞中纯化出来,并且其许多生化特性已被表征。DNA-PK由一个大的催化亚基DNA-PKcs和一个DNA靶向蛋白Ku组成。当组装在合适的DNA分子上时,DNA-PK全酶作为丝氨酸/苏氨酸蛋白激酶,其在体外磷酸化许多DNA结合和非结合蛋白以及转录因子。最近的遗传学研究强烈指出在DNA双链断裂修复和V(D)J重组中的功能。此外,生物化学研究表明在转录调节中的作用。在这里,我们讨论,从历史的角度来看,导致我们目前的理解DNA-PK的功能的事件,包括最近的结果,从我们自己的研究表明,参与细胞凋亡和DNA-PK。在病毒感染人体细胞方面。
The phenomenon of DNA-dependent protein phosphorylation was first described little over 10 years ago. Since then a DNA-dependent protein kinase, DNA-PK, has been purified from human cells and many of its biochemical properties have been characterized. DNA-PK is composed of a large catalytic subunit, DNA-PKcs, and a DNA-targeting protein, Ku. When assembled on a suitable DNA molecule, the DNA-PK holoenzyme acts as a serine/threonine protein kinase that in vitro phosphorylates many DNA binding and non-binding proteins and transcription factors. Recent genetic studies point strongly to functions in DNA double-strand break repair and V(D)J recombination. In addition, biochemical studies suggest a role in the regulation of transcription. Here we discuss, from a historical perspective, the events leading up to our current understanding of the function of DNA-PK, including recent results from our own studies suggesting the involvement of DNA-PK in apoptosis and. in viral infection of human cells.