泛素、泛素链和蛋白质泛素化研究进展

Progress in ubiquitin, ubiquitin chain and protein ubiquitination

摘要:

蛋白质泛素化是以泛素单体和泛素链作为信号分子，共价修饰细胞内其他蛋白质的一种翻译后修饰形式。不同蛋白质底物、同一底物的不同氨基酸修饰位点以及同一位点上泛素链连接方式的不同均可导致细胞效应的差异。蛋白质泛素化在真核细胞内广泛存在，除了介导蛋白质的26S蛋白酶体降解途径之外，还广泛参与了基因转录、蛋白质翻译、信号传导、细胞周期控制以及生长发育等几乎所有的生命活动过程。泛素链的形成及其修饰过程的任何失调均可导致生物体内环境的紊乱，从而产生严重的疾病。文中结合实验室研究，综述了泛素的发现历史、基因特点、晶体结构，特别是泛素链的组装过程、结构、功能以及与人类相关疾病关系的新进展，可为这些疾病的治疗靶点和药物靶标的研究提供思路。

Abstract:

Protein ubiquitination is one of the most important and widely exist protein post-translational modifications in eukaryotic cells, which takes the ubiquitin and ubiquitin chains as signal molecules to covalently modify other protein substrates. It plays an important roles in the control of almost all of the life processes, including gene transcription and translation, signal transduction and cell-cycle progression, besides classical 26S protesome degradation pathway. Varied modification sites in the same substrates as well as different types of ubiquitin linkages in the same modification sites contain different structural information, which conduct different signal or even determine the fate of the protein substrates in the cell. Any abnormalities in ubiquitin chain formation or its modification process may cause severe problem in maintaining the balance of intracellular environment and finally result in serious health problem of human being. In this review, we discussed the discovery, genetic characteristics and the crystal structure of the ubiquitin. We also emphasized the recent progresses of the assembly processes, structure and their biological function of ubiquitin chains. The relationship between the disregulation and related human diseases has also been discussed. These progress will shed light on the complexity of proteome, which may also provide tools in the new drug research and development processes.