FUNCTION AND REGULATION OF PHOSPHORYLATED BC1-2

描述（申请人描述）：研究者为临床 病理学家在西北大学医学院早期的学术实践 学校的主要研究兴趣在分子生物学的 癌蛋白Bcl-2。 这个机构已经证明了一个特殊的 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·Lurie癌症中心联合了236个基础和 临床研究者 已招募调查员， 独立的基础研究实验室，专注于Bcl-2的作用， 癌蛋白在肿瘤发生中的作用 申请人的研究计划摘要如下。 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， 确保多余或不需要的细胞被清除。 这个过程是 在治疗癌症方面也具有重要意义，因为大多数 化疗剂通过诱导细胞凋亡而起作用。 癌蛋白， 在许多情况下，Bcl-2可以阻断或延迟凋亡，并且当Bcl-2在细胞中表达时， 恶性细胞常常使化疗无效。 Bcl-2也可以减缓 细胞周期进展，但尚不清楚这种影响是否与 Bcl-2的抗凋亡作用。 调查人员现在已经观察到， Bcl-2可以延迟细胞周期进程， 凋亡，Bcl-2的这种特性可能依赖于其 磷酸化状态。 根据他们的初步数据， 生理（抗凋亡和抗增殖）与促癌 (only Bcl-2的抗凋亡机制是由其 磷酸化 在这份拨款申请中，他们希望研究 Bcl-2延缓细胞周期进程的作用， Bcl-2在细胞周期和凋亡调控中的作用，并鉴定和表征 Bcl-2激酶蛋白。

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.