Gottlieb T M, Jackson S P
Wellcome/CRC Institute, Cambridge, England.
Cell. 1993 Jan 15;72(1):131-42. doi: 10.1016/0092-8674(93)90057-w.
The DNA-dependent protein kinase (DNA-PK) phosphorylates Sp1 and several other nuclear proteins. Here, we show that Sp1 and the DNA-PK must be colocalized on the same DNA molecule for efficient phosphorylation to occur. Interestingly, we find that the DNA-PK binds to and is activated by the ends of DNA molecules. Furthermore, we show that the DNA binding properties of the DNA-PK are identical to those of Ku, a well-characterized human autoimmune antigen. We demonstrate that the DNA-PK can be fractionated into two components, one of which is Ku and the other of which is a polypeptide of approximately 350 kd. DNA cross-linking and coimmunoprecipitation studies indicate that the catalytic 350 kd DNA-PK component is directed to DNA by protein-protein interactions with Ku. The implications of the unusual DNA binding mode and multicomponent nature of the DNA-PK are discussed.
DNA依赖性蛋白激酶（DNA-PK）可使Sp1及其他几种核蛋白发生磷酸化。在此，我们发现Sp1与DNA-PK必须共定位于同一DNA分子上，才能高效发生磷酸化。有趣的是，我们发现DNA-PK与DNA分子末端结合并被其激活。此外，我们表明DNA-PK的DNA结合特性与Ku相同，Ku是一种特征明确的人类自身免疫抗原。我们证明DNA-PK可分为两个组分，其中一个是Ku，另一个是约350kd的多肽。DNA交联和共免疫沉淀研究表明，具有催化活性的350kd DNA-PK组分通过与Ku的蛋白质-蛋白质相互作用被导向DNA。文中讨论了DNA-PK不同寻常的DNA结合模式和多组分性质的意义。
