FUNCTION AND REGULATION OF PHOSPHORYLATED BC1-2

描述(申请人描述)：调查员是一名临床医生 西北大学医学院早期学术实践中的病理学家 主要研究人脑的分子生物学的学校 癌蛋白Bc l-2。这个机构展示了一种特殊的 致力于在癌症研究中发展强大的多学科计划 通过建立罗伯特·H·卢里癌症中心，将236个基础和 临床研究人员。调查员已被招募来开发一种 专注于Bcl-2作用的独立基础研究实验室 癌蛋白在肿瘤发生中的作用 以下是申请者研究计划的摘要。 细胞凋亡，或程序性细胞死亡，是细胞自杀的一种活跃形式 在各种生理和发育系统中发挥作用 确保消除多余或不需要的单元格。这个过程是 在治疗癌症方面也具有重要意义，因为大多数 化疗药物通过诱导细胞凋亡发挥作用。癌蛋白， BCL-2在许多情况下可以阻断或延缓细胞凋亡，当表达在 恶性细胞常常使化疗无效。BCL-2也可以减慢 细胞周期进程，但目前尚不清楚这种影响是否与 Bcl-2‘S抗细胞凋亡作用。调查人员现在观察到， Bcl2可以独立于其对细胞周期的影响而延缓细胞周期进程 Bcl2的这一特性可能依赖于其 磷酸化状态。根据他们的初步数据，他们假设 生理性(抗细胞凋亡和抗增殖)与促肿瘤 (仅限抗细胞凋亡)Bcl2的机制是由其决定和调节的 磷酸化。在这份赠款提案中，他们希望研究这一机制 其中bc l-2通过延缓细胞周期进程、磷酸化的作用 BCL-2在细胞周期和细胞凋亡调控中的作用 Bc l-2蛋白。

DESCRIPTION (Applicant's Description): The investigator is a clinical pathologist in early academic practice at Northwestern University Medical School with primary research interest in the molecular biology of the oncoprotein Bcl-2. This institution has demonstrated an exceptional commitment to develop a strong multidisciplinary program in cancer research by establishing the Robert H. Lurie Cancer Center that unites 236 basic and clinical researchers. The investigator has been recruited to develop an independent basic research laboratory focusing on the role of the Bcl-2 oncoprotein in tumorigenesis. A summary of the applicant's research plan follows. Apoptosis, or programmed cell death, is an active form of cellular suicide that functions in a variety of physiological and developmental systems to ensure that superfluous or unwanted cells are eliminated. This process is also of great significance in the treatment of cancer, as most chemotherapeutic agents function by inducing apoptosis. The oncoprotein, Bcl-2 can block or delay apoptosis in many instances, and when expressed in malignant cells often renders chemotherapy ineffective. Bcl-2 can also slow cell cycle progression, but it is not known if this effect is related to Bcl-2's apoptosis countering function. The investigators have now observed, that Bcl-2 can delay cell cycle progression independently of its effect on apoptosis, and that this property of Bcl-2 may be dependent on its phosphorylation status. Based on their preliminary data they hypothesize that the physiologic (antiapoptotic and antiproliferative) vs. pro-oncogenic (only antiapoptotic) mechanism of Bcl-2 is determined and regulated by its phosphorylation. In this grant proposal they wish to examine the mechanism by which Bcl-2 delay cell cycle progression, the role of phosphorylated Bcl-2 in cell cycle and apoptosis regulation, and identify and characterize the Bcl-2 kinase protein.