Petroski Matthew D
Rigel Pharmaceuticals, Inc, South San Francisco, CA, 94080, USA.
BMC Biochem. 2008 Oct 21;9 Suppl 1(Suppl 1):S7. doi: 10.1186/1471-2091-9-S1-S7.
The ubiquitin system of protein modification has emerged as a crucial mechanism involved in the regulation of a wide array of cellular processes. As our knowledge of the pathways in this system has grown, so have the ties between the protein ubiquitin and human disease. The power of the ubiquitin system for therapeutic benefit blossomed with the approval of the proteasome inhibitor Velcade in 2003 by the FDA. Current drug discovery activities in the ubiquitin system seek to (i) expand the development of new proteasome inhibitors with distinct mechanisms of action and improved bioavailability, and (ii) validate new targets. This review summarizes our current understanding of the role of the ubiquitin system in various human diseases ranging from cancer, viral infection and neurodegenerative disorders to muscle wasting, diabetes and inflammation. I provide an introduction to the ubiquitin system, highlight some emerging relationships between the ubiquitin system and disease, and discuss current and future efforts to harness aspects of this potentially powerful system for improving human health. PUBLICATION HISTORY : Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
蛋白质修饰的泛素系统已成为参与调控多种细胞过程的关键机制。随着我们对该系统中各途径的了解不断深入，蛋白质泛素与人类疾病之间的联系也日益紧密。2003年，蛋白酶体抑制剂万珂（Velcade）获美国食品药品监督管理局（FDA）批准，泛素系统在治疗方面的潜力得以彰显。目前，针对泛素系统的药物研发活动旨在：（i）拓展具有独特作用机制和更高生物利用度的新型蛋白酶体抑制剂的开发；（ii）验证新的靶点。本综述总结了我们目前对泛素系统在从癌症、病毒感染、神经退行性疾病到肌肉萎缩、糖尿病和炎症等各种人类疾病中所起作用的理解。我将介绍泛素系统，强调泛素系统与疾病之间一些新出现的关系，并讨论当前及未来利用这一潜在强大系统的各个方面来改善人类健康的努力。发表历史：转载自Current BioData的靶向蛋白质数据库（TPdb；http://www.targetedproteinsdb.com）。
