Cell Cycle and Cancer Unit, St Vincent's Institute of Medical Research, The University of Melbourne, Fitzroy, Melbourne, Victoria 3065, Australia.
Biosci Rep. 2010 Mar 17;30(4):243-55. doi: 10.1042/BSR20090171.
The eukaryotic cell cycle is a fundamental evolutionarily conserved process that regulates cell division from simple unicellular organisms, such as yeast, through to higher multicellular organisms, such as humans. The cell cycle comprises several phases, including the S-phase (DNA synthesis phase) and M-phase (mitotic phase). During S-phase, the genetic material is replicated, and is then segregated into two identical daughter cells following mitotic M-phase and cytokinesis. The S- and M-phases are separated by two gap phases (G1 and G2) that govern the readiness of cells to enter S- or M-phase. Genetic and biochemical studies demonstrate that cell division in eukaryotes is mediated by CDKs (cyclin-dependent kinases). Active CDKs comprise a protein kinase subunit whose catalytic activity is dependent on association with a regulatory cyclin subunit. Cell-cycle-stage-dependent accumulation and proteolytic degradation of different cyclin subunits regulates their association with CDKs to control different stages of cell division. CDKs promote cell cycle progression by phosphorylating critical downstream substrates to alter their activity. Here, we will review some of the well-characterized CDK substrates to provide mechanistic insights into how these kinases control different stages of cell division.
真核细胞周期是一个基本的进化保守过程，它调节从简单的单细胞生物（如酵母）到高等多细胞生物（如人类）的细胞分裂。细胞周期包括几个阶段，包括 S 期（DNA 合成期）和 M 期（有丝分裂期）。在 S 期，遗传物质被复制，然后在有丝分裂 M 期和胞质分裂后分配到两个相同的子细胞中。S 期和 M 期之间被两个间隙期（G1 和 G2）隔开，它们控制着细胞进入 S 期或 M 期的准备状态。遗传和生化研究表明，真核生物的细胞分裂是由 CDK（细胞周期蛋白依赖性激酶）介导的。活性 CDK 由蛋白激酶亚基组成，其催化活性依赖于与调节性细胞周期蛋白亚基的结合。不同细胞周期蛋白亚基在细胞周期不同阶段的积累和蛋白水解降解调节它们与 CDK 的结合，以控制细胞分裂的不同阶段。CDK 通过磷酸化关键下游底物来促进细胞周期进程，从而改变其活性。在这里，我们将回顾一些特征明确的 CDK 底物，以提供这些激酶如何控制细胞分裂不同阶段的机制见解。
