From Cdc2 to Cdk1: when did the cell cycle kinase join its cyclin partner?
From Cdc2 to Cdk1: when did the cell cycle kinase join its cyclin partner?
复制标题
DOI：
--
复制
发表时间：
2002-06
影响因子：
4
通讯作者：
M. Dorée;T. Hunt
中科院分区：
文献类型：
--
作者：
M. Dorée;T. Hunt
Cdc 2和细胞周期蛋白在控制细胞周期的G2/M转换中起关键作用的想法主要来自对裂殖酵母的遗传分析以及对蛤、蛙、海胆和海星卵和卵母细胞的生理学研究。然而，花了很长时间才意识到Cdc 2和细胞周期蛋白形成化学计量复合物，并且细胞周期蛋白亚基是Cdc 2亚基获得其蛋白激酶活性所必需的。细胞周期蛋白最初被认为是在海洋无脊椎动物卵的早期细胞周期中丰度振荡的蛋白质，并且它们与MPF（促成熟因子）的联系最初还很不清楚，MPF是在青蛙和海星卵母细胞中定义的实体，其活性控制进入M期。事实上，在MPF被证明是一种蛋白激酶之前已经过了很长时间，并且只有当纯化的海星MPF的Cdc 2相关组分被测序并发现是细胞周期蛋白B时，才最终获得MPF是包含一个细胞周期蛋白分子和一个Cdc 2分子的异源二聚体的直接证据。当这一基本发现在脊椎动物中得到证实时，Cdc 2家族的哺乳动物成员也被证明与细胞周期蛋白结合，Cdc 2成为第一个细胞周期蛋白依赖性蛋白激酶Cdk 1。
The idea that Cdc2 and cyclins play a key role in the control of the G2/M transition of the cell cycle came largely from genetic analysis of fission yeast and physiological studies of clam, frog, sea urchin and starfish eggs and oocytes. However, it took a long time to realise that Cdc2 and cyclins form a stoichiometric complex and that a cyclin subunit is necessary for the Cdc2 subunit to gain its protein kinase activity. Cyclins were first recognized as proteins whose abundance oscillates during the early cell cycles of marine invertebrate eggs and their connection with MPF (maturation-promoting factor), the entity defined in frog and starfish oocytes whose activity controls entry into M phase, was far from clear at first. Indeed, it was a long time before MPF was shown to be a protein kinase, and direct proof that MPF is a heterodimer comprising one molecule of cyclin and one molecule of Cdc2 was finally obtained only when the Cdc2-associated component of purified starfish MPF was sequenced and found to be cyclin B. When this fundamental discovery was confirmed in vertebrates and mammalian members of the Cdc2 family were also shown to bind cyclins, Cdc2 became Cdk1, the first cyclin-dependent protein kinase.