Cell cycle block by HMG co-A reductase inhibitors

HMG co-A 还原酶抑制剂阻断细胞周期

• 批准号: 6801016
• 负责人: Chinweike Ukomadu
• 金额: $ 13.39万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6801016
• 关键词: HMG coA reductases; SDS polyacrylamide gel electrophoresis; cell cycle; cell growth regulation; cell line; cell proliferation; cyclin dependent kinase; enzyme activity; enzyme substrate; flow cytometry; lovastatin; oncoprotein p21; oxidoreductase inhibitor; phosphorylation; plasmids; transfection /expression vector; western blottings

DESCRIPTION (provided by applicant): This application is intended to provide outstanding mentorship and a supportive laboratory environment to foster the development of Chinweike Ukomadu, M.D., Ph.D., towards a career as an independent scientist. The candidate has completed graduate studies and published several papers in the field of ion channel physiology. Following clinical training in internal medicine and gastroenterology he returned to the laboratory to study mechanisms of cell cycle regulation. The proposed research will be carried out in the laboratory of Anindya Dutta, M.D., Ph.D., an internationally recognized investigator in the area of cell cycle regulation. Dr. Dutta's record in mentoring numerous junior scientists as they transitioned to careers as principal investigators provides an ideal setting for implementation of the goals of this proposal. Dr. Dutta's laboratory has extensive expertise in cell biological, biochemical, and genetic methodologies related to cell cycle studies. Seminars, conferences, and collegial interactions within the Departments of Pathology and Internal Medicine at Brigham and Women's Hospital will offer additional opportunity for scientific and career development. This proposal outlines detailed studies aimed at further understanding the regulation of cyclin dependent kinase 2 (Cdk2), a key enzyme required for progression through the cell cycle. The studies will be carried out using established cancer cell lines. In preliminary studies, mevastatin, a cholesterol lowering agent, inhibited Cdk2 by preventing activating phosphorylation. The specific aims are: 1) to determine the molecular mechanism by which mevastatin inhibits the activation of Cdk2; 2) to show that cyclin H:cdk7, which has been felt to be essential for activation of Cdk2, is not required in some cancer cell lines; and 3) to elucidate the events underlying the inability of p21 to inhibit Cdk2 in some cancer cells.

描述（申请人提供）：本申请旨在提供优秀的指导和支持性的实验室环境，以促进Chinweike Ukomadu医学博士的发展，成为一名独立的科学家。该候选人在离子通道生理学领域完成了研究生学习并发表了多篇论文。在接受了内科和胃肠病学的临床培训后，他回到实验室研究细胞周期调节的机制。