小G蛋白泛素化分子机制研究

项目名称： 小G蛋白泛素化分子机制研究

项目编号： No.31500631

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 王梅林

作者单位： 河南科技大学

项目金额： 20万元

中文摘要： 小G蛋白家族成员众多，它们作为分子开关，在细胞内众多的生理生化调节过程中起着关键作用。文献报导泛素化修饰通过介导某些小G蛋白的降解过程进而调控其生理功能，然而绝大部分成员泛素化修饰的分子机制尚无研究。本项目通过克隆小G蛋白家族150个成员基因（已克隆超过100个基因），将其与Nedd4类泛素连接酶共转染，筛选介导小G蛋白泛素化修饰的E3泛素连接酶（初步结果见工作基础），并解析其被泛素化的分子机理；探索泛素化修饰作为一种普遍的调控机制，通过调控小G蛋白的表达水平与活性，进而参与调控细胞中多种信号通路和生理生化过程。该项目将为我们系统性地揭示小G蛋白的泛素化修饰情况，其研究的深入将帮助我们认识癌症发生发展的机理。

中文关键词： 小G蛋白；泛素化修饰；泛素连接酶；调控机制

英文摘要： Small G proteins act as molecular switches in regulating a wide variety of cellular physiological and biochemical functions. Papers reported several small G proteins are targeted for ubiquitination and degradation, thus regulating their biological functions. However most of them is unreported being ubiquitylated. In our study, we aim to clone this 150 member genes of Small G protein superfamily (have successfully cloned over 100 genes), screen the responsible E3 ubiquitin ligase(s) by co-transfecting them with E3 ubiquitin ligases of Nedd4-like family ( preliminary results see the work foundation part) and further study the mechanism of ubiquitination-mediated regulation of small G proteins. We next aim to explore how ubiquitylation modification works as a mechanism in participating many small G protein involved signaling pathways and regulating multiple cellular biological functions. Our study would provide us a general picture of ubiquitylation modification of Small G protein superfamily, and as reseach continues, it would help us with our understanding of tumorigenesis.

英文关键词： small G protein;ubiquitination modification;E3 ligase;regulatory mechanism