The Function of Cdk1/cyclin B in Mitotic Entry.

描述（由申请人提供）： 不受控制的细胞分裂是癌症的标志。虽然在破译肿瘤发生的分子基础方面取得了很大进展，但对细胞周期进程复杂性的更深入理解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高度调节的步骤，因此，参与这一过程的一些蛋白质在人类癌症中是靶向的。因此，有丝分裂进入机制的基础研究是癌症研究的重要组成部分。本研究的目的是：1）确定Cdkl/细胞周期蛋白B对有丝分裂进入的贡献，以及2）鉴定和表征驱动脊椎动物细胞周期从G2期到M期转变的Cdkl/细胞周期蛋白B的新底物。将使用化学遗传筛选来鉴定Cdkl/细胞周期蛋白B复合物的一组全面的蛋白质底物。将使用细胞生物学和生物化学方法的组合表征底物在细胞周期进展中的作用。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Cdkl/细胞周期蛋白B活性的升高最终如何驱动进入有丝分裂。

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.