The Function of Cdk1/cyclin B in Mitotic Entry.

Cdk1/cyclin B 在有丝分裂进入中的功能。

• 批准号: 6694398
• 负责人: SUSANNE M STEGGERDA
• 金额: $ 4.73万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6694398
• 关键词: Xenopus oocyte; cell cycle; cell growth regulation; cyclin dependent kinase; cyclins; cytogenetics; enzyme activity; enzyme substrate; gel electrophoresis; immunoprecipitation; mass spectrometry; mitotic spindle apparatus; molecular biology information system; phosphorylation; postdoctoral investigator; protein localization; protein structure function; radiotracer

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.

描述（由申请人提供）： 不受控制的细胞分裂是癌症的一个标志。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，但对于开发新的治疗策略，需要更深入地了解细胞周期进展的复杂性。从 G2 期到 M 期的转变是细胞分裂周期中受到高度调控的步骤，因此，参与此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癌症研究的重要组成部分。本研究的目标是：1) 确定 Cdkl/cyclin B 对有丝分裂进入的贡献，2) 识别和表征驱动脊椎动物细胞从 G2 期向 M 期转变的 Cdkl/cyclin B 新型底物循环。将使用化学遗传筛选来鉴定 Cdk1/细胞周期蛋白 B 复合物的一套全面的蛋白质底物。将结合细胞生物学和生化方法来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 晚期 Cdk1/细胞周期蛋白 B 活性的上升如何最终驱动进入有丝分裂。