酵母RNA聚合酶II羧基端结构域激酶CTDK-I及其亚基的结构与功能

Structure and function of yeast RNA polymerase II carboxyl-terminal repeat domain kinase CTDK-I and its subunits

摘要:

RNA聚合酶Ⅱ最大亚基Rpb1的羧基端结构域（carboxyl-terminal repeat domain，CTD）是RNA聚合酶Ⅱ发挥转录延伸功能所必需的，对其执行精确的转录调节功能至关重要。酵母细胞周期蛋白依赖性激酶CTDK-I（carboxyl-terminal repeat domain kinase，CTDK-I）由CTK1、CTK2和CTK3组成，作用于RNA聚合酶Ⅱ羧基端结构域，动态磷酸化CTD的七肽重复序列（YSPTSPS）来调控转录和翻译。酵母中的特异性蛋白CTK3与特殊的细胞周期蛋白CTK2结合形成异二聚体，再与CTDK-I的催化亚基CTK1结合以调节其活性。CTK1作为细胞周期蛋白CDK（cyclin dependent kinase，CDK）的同源蛋白，其结构与功能的研究可拓展人们对CDK蛋白家族的认识；CTK2-CTK3复合物对CTK1调控机制的研究也可为细胞周期蛋白抑制剂的研发提供新的思路。本文简述了酵母CTDK-I的功能特点及其亚基的结构与功能以及亚基间的相互作用，并展望了CTDK-I复合物的研究前景。

Abstract:

Carboxyl-terminal repeat domain (CTD) of RNA polymerase Ⅱ largest subunit Rpb1 is essential for transcription regulation. Carboxyl-terminal repeat domain kinase (CTDK-I) is composed of CTK1, CTK2 and CTK3, acting on RNA polymerase Ⅱ carboxyl-terminal repeat domain and phosphorylating CTD heptapeptide repeat (YSPTSPS) for regulating transcription and translation. The specific protein CTK3 binds to cyclin CTK2 to form a heterodimer, controlling CTK1 activity by binding to CTK1. Structural and functional study of CTK1, a homologous protein of cyclin dependent kinase (CDK), may provide a new idea for the research of CDK family, and analysis of the regulatory mechanism of activation of CTK1 by CTK2-CTK3 complex may offer an innovative method for developing cell cycle protein inhibitors. This article reviews the functional characteristics of CTDK-I and the structures and interactions of its subunits and provides a useful guide for the studies of CTDK-I complex in the future.