F-box蛋白CG5003介导的泛素化修饰调控果蝇发育的机制研究

项目名称： F-box蛋白CG5003介导的泛素化修饰调控果蝇发育的机制研究

项目编号： No.31270825

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 何淑君

作者单位： 同济大学

项目金额： 80万元

中文摘要： 蛋白质稳定性的调节主要来自两个途径：蛋白质合成（protein synthesis）以及蛋白质降解（protein degradation），取得合成与降解之间的平衡，从而控制蛋白质的质与量，是非常重要的调节机制，影响蛋白质网络的动态平衡，生物体内的发育过程及不同功能。降解通路中的许多蛋白，也是临床药物设计中热门的靶蛋白。由F-box蛋白介导的泛素化修饰机制为蛋白质降解提供了重要的理论基础与支持，也为蛋白质治疗提供了前瞻性的思路。本项目研究一个新型的F-box蛋白CG5003，利用果蝇模式生物简易的遗传操作手段，配合生化技术，鉴定他的底物以及相互作用的蛋白，以机理分明的翅膀发育和影响爬行能力的神经肌肉接头突触为模型，分析CG5003对这些系统发育与功能的调节，阐明影响的信号转导通路，研究CG5003介导的泛素化修饰调节蛋白质稳定性与动态平衡的分子机制，为蛋白质治疗提供崭新想法与新型策略。

中文关键词： 泛素化；蛋白质降解；F-box蛋白；神经肌肉接头；果蝇模式生物

英文摘要： Protein synthesis and protein degradation are the two major routes for maintaining a stable network of protein dynamics at any given time and location. Understanding how proteins are degraded is important for developing novel drug targets for disease pertaining protein stability and dynamics. Among all, ubiquitination-mediated 26S proteasome degradation is the most prominent pathway for degrading a target protein. F-box proteins, the substrate recognition component in this pathway, are significant players and provide the substrate specificity in determining which protein to be degraded. Here we propose to study a novel F-box protein, CG5003, in the animal organism Drosophila. Loss-of-function studies indicate that CG5003 is required for fly survival, wing development, and the neuromuscular junction (NMJ) function. Biochemical approaches such as coimmuonoprecipitation and mass spectrometry will be used to identify substrates and interacting partners for CG5003. In addition to define the molecular composition of CG5003, potential biological pathways that CG5003 participates in will be identified via studies in two systems: wing and NMJ development. These studies will provide novel insights on how CG5003 mediates ubiquitination and degradation and how its actions are relevant in a developmental or functional contex

英文关键词： Ubiquitination；Protein Degradation；F-box；NMJ；Drosophila