蛋白质组学在去泛素化酶研究中的应用

Application of proteomics in deubiquitinases research

摘要:

泛素-蛋白酶体系统是细胞内蛋白质特异性降解的主要途径，参与并调控细胞周期、免疫应答、信号传递和DNA修复等真核生物体内几乎所有的生命活动。去泛素酶的存在使泛素化修饰成为可逆过程，保证了泛素系统及其相关生理过程的动态平衡，其表达紊乱也是诱发多种疾病的主要原因。对去泛素化酶进行系统、全面的研究是理解其作用机制并将其作为治疗药物靶点的前提。蛋白质组学技术的快速发展为系统深入研究去泛素化酶提供了条件，特别是在去泛素化酶的相互作用网络和底物特异性研究等方面发挥了独特的作用。因此，文中结合课题组研究工作，对去泛素化酶的分类及功能进行介绍并总结蛋白质组学在去泛素化酶研究中的应用进展。

关键词:泛素-蛋白酶体系统，去泛素化酶，蛋白质组学，蛋白质相互作用，质谱

Abstract:

As the major pathway mediating specific protein degradation in eukaryotes, ubiquitin-proteasome system (UPS) is involved in various physiological and pathological processes such as cell cycle regulation, immune response, signal transduction and DNA-repair. Deubiquitinases (DUB) maintain the balance of UPS and related physiological processes via reversibly removing ubiquitin from the covalently modified protein substrates, which have been implicated in various disease processes in case of their imbalance expression. Because DUB plays critical regulating roles in the UPS pathway, they may be also the ideal drug targets for severe and intractable human diseases, such as cancer and neurodegenerative disease. With the rapid development of proteomic technology, systematical investigation of specific substrates and interacting proteins of varied DUB via mass spectrometry approach may shed light on these DUB’s biological function and regulating roles in the physiological and pathogenic states. In this review, we briefly introduce the characteristics of DUB and summarize the recent application and progresses of proteomics in DUB research.

Key words:ubiquitin-proteasome system, deubiquitinase, proteomics, interactome , mass spectrometry