Zhao J, Dynlacht B, Imai T, Hori T, Harlow E
Laboratory of Molecular Oncology, Massachusetts General Hospital (MGH) Cancer Center, Charlestown, Massachusetts 02129, USA.
Genes Dev. 1998 Feb 15;12(4):456-61. doi: 10.1101/gad.12.4.456.
To understand the mechanisms by which CDKs regulate cell cycle progression, it is necessary to identify and characterize the physiological substrates of these kinases. We have developed a screening method to identify novel CDK substrates. One of the cDNAs identified in the screen is identical to the recently isolated NPAT gene. Here we show that NPAT associates with cyclin E-CDK2 in vivo and can be phosphorylated by this CDK. The protein level of NPAT peaks at the G1/S boundary. Overexpression of NPAT accelerates S-phase entry, and this effect is enhanced by coexpression of cyclin E-CDK2. These results suggest that NPAT is a substrate of cyclin E-CDK2 and plays a role in S-phase entry.
为了理解细胞周期蛋白依赖性激酶（CDKs）调节细胞周期进程的机制，有必要鉴定并表征这些激酶的生理底物。我们开发了一种筛选方法来鉴定新的CDK底物。在筛选中鉴定出的一个cDNA与最近分离出的NPAT基因相同。在此我们表明，NPAT在体内与细胞周期蛋白E-CDK2结合，并且可以被这种CDK磷酸化。NPAT的蛋白水平在G1/S边界达到峰值。NPAT的过表达加速S期进入，并且细胞周期蛋白E-CDK2的共表达增强了这种效应。这些结果表明，NPAT是细胞周期蛋白E-CDK2的底物，并在S期进入中发挥作用。
