The Function of Cdk1/cyclin B in Mitotic Entry.

描述(由申请人提供)： 细胞分裂失控是癌症的一个标志。尽管在破译肿瘤发生的分子基础方面已经取得了很大进展，但深入了解细胞周期进程的复杂性对于开发新的治疗策略是必要的。从G2期到M期的转变是细胞分裂周期中一个高度受调控的步骤，因此，参与这一过程的一些蛋白质是人类癌症的靶标。因此，有丝分裂进入机制的基础研究是肿瘤研究的重要组成部分。本研究的目的是：1)确定CDK1/Cyclin B在有丝分裂进入过程中的作用；2)鉴定和鉴定驱动脊椎动物细胞周期从G2期向M期转变的新的CDK1/Cyclin B底物。将使用化学遗传筛选来确定CDK1/细胞周期蛋白B复合体的一套全面的蛋白质底物。我们将结合细胞生物学和生物化学的方法，对底物在细胞周期进程中的作用进行表征。这些研究的结果将有助于更详细地了解早期有丝分裂的事件，包括G2期晚期CDK1/Cyclin B活性的增加如何最终推动进入有丝分裂。

DESCRIPTION (provided by applicant): Uncontrolled cell division is a hallmark of cancer. Although much progress has been made in deciphering the molecular basis of tumorigenesis, a deeper understanding of the complexities of cell cycle progression will be necessary for the development of novel therapeutic strategies. The transition from G2 to M phase is a highly regulated step in the cell division cycle, and as such, some proteins involved in this process are targeted in human cancers. Thus, basic research on the mechanism of mitotic entry is an important part of cancer research. The goals of this research are: 1) to define the contribution of Cdkl/cyclin B towards mitotic entry, and 2) to identify and characterize novel substrates of Cdkl/cyclin B that drive the transition from G2 phase to M phase of the vertebrate cell cycle. A chemical-genetic screen will be used to identify a comprehensive set of protein substrates for the Cdkl/cyclin B complex. Substrates will be characterized for their roles in cell cycle progression using a combination of cell biological and biochemical methods. Results from these studies will contribute toward a more detailed understanding of the events of early mitosis, including how the rise of Cdkl/cyclin B activity during late G2 phase ultimately drives entry into mitosis.