STRUCTURE/FUNCTION STUDY OF CDC34

CDC34的结构/功能研究

• 批准号: 2101311
• 负责人: CALVIN N STEUSSY
• 金额: $ 5.32万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-02-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2101311
• 关键词: Saccharomyces cerevisiae; X ray crystallography; cell cycle proteins; chemical conjugate; chemical kinetics; enzyme mechanism; enzymes; fungal genetics; molecular cloning; oncogenes; point mutation; protein structure function; recombinant proteins; transcription factor; ubiquitin

The goal of this application for the NCI Clinical Investigator Award is to provide a transition for Dr. Steussy from his successful clinical career as a family practitioner to that of a scientifically qualified clinical investigator. The proposed project is to uncover the structure/function relationships of the yeast ubiquitin conjugating enzyme Cdc34 and it recently cloned human equivalent. The specific hypothesis is that knowledge of the three dimensional structure and kinetic parameters of normal Cdc34 and some critical point mutations will illuminate the chemical mechanism and control of this vital cell cycle enzyme. The proposed study is significant because Cdc34 is an incompletely understood enzyme that performs an essential role in the normal cell cycle and as a downstream effector for the oncogene p53. A complete understanding of this enzyme is fundamental to understanding normal cell cycle control and the etiology of carcinogenesis. After five years in rural clinical practice Dr. Steussy has elected to begin a career in scientific research. His M.D. was granted by Indiana University in 1981, and he completed a residency in Family Practice at the University of Minnesota in 1984. After five years of engaging clinical practice in an underserved area of rural Tennessee he began graduate study here at Indiana University. In the last two and a half years he has made substantial progress on cloning and purifying Cdc34, cloning and purifying its upstream activator E1, and developing an activity assay. In order to bring his scientific fund of knowledge up to date he completed the core classroom requirements of the Department of Biochemistry for the Ph.D. degree and passed the departmental qualifying exam. Much of the strength of this project comes from its particular sponsors and the Department of Biochemistry. The sponsors, Dr. Goebl and Dr. Hamilton, are both experienced and well respected in their fields. Outstanding educators as well as extensively published researchers they make a superb team to guide Dr. Steussy through this project and see to his training as a competent independent investigator

NCI临床研究者奖的该申请的目的是 从成功的临床上为Steussy博士提供过渡 作为一名科学资格的家庭从业者的职业 临床研究者。 拟议的项目是发现 酵母泛素结合的结构/功能关系 酶CDC34及其最近克隆的人类当量。 具体 假设是三维结构的知识和 正常CDC34和一些临界点突变的动力学参数将 阐明该重要细胞周期的化学机制和控制 酶。 拟议的研究很重要，因为cdc34是 不完全理解的酶在 正常的细胞周期，作为癌基因p53的下游效应子。 一个 完全了解该酶是理解的基础 正常的细胞周期控制和致癌的病因。 经过五年的农村临床实践，Steussy博士选择了 开始科学研究的职业。 他的医学博士由印第安纳州授予 1981年的大学，他在 明尼苏达大学于1984年。参与了五年之后 在田纳西州农村地区服务不足的地区，他开始 印第安纳大学的研究生学习。 在最后两个半中 多年以来，他在克隆和净化Cdc34方面取得了长足进展， 克隆和纯化其上游激活剂E1，并开发一个 活动测定。 为了提高他的科学知识基金 迄今为止，他完成了部门的核心课堂要求 博士生物化学学位并通过了部门 合格考试。 该项目的大部分优势来自其特定的赞助商 和生物化学系。 赞助商Goebl博士和博士 汉密尔顿在他们的领域都经验丰富且受到尊重。 杰出的教育者以及广泛发表的研究人员 组成一支精湛的团队，指导Steussy博士完成这个项目，并查看 他作为合格的独立调查员的培训