Tanaka Keiji
Laboratory of Frontier Science, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2006 Apr;26(2):67-73.
There are growing lines of evidence addressing the importance of the ubiquitin-proteasome system (UPS) that catalyzes various biological reactions rapidly, methodically, exhaustively, and unidirectionally. UPS is responsible for a diverse array of biologically important cellular processes, such as cell-cycle progression, signaling cascades and developmental programs. This system is also involved in the protein quality control, which maintains the homeostasis of the cell. Of particular interest is that UPS provides a clue for understanding of the molecular mechanisms underlying various neurodegenerative diseases. In the last decade, we witnessed a tremendous progress in uncovering the mechanisms of Parkinson's disease (PD). Of the several genes that can cause familial PD, parkin, the causative gene of autosomal recessive juvenile parkinsonism (AR-JP), is of a special interest because it encodes an ubiquitin-protein ligase, which covalently attaches ubiquitin to target proteins, designating them for destruction by the proteasome (a eukaryotic ATP-dependent protease complex). This review summarizes recent studies on the UPS pathway with a special reference to parkin, focusing on how parkin is linked to the pathogenesis of AR-JP.
越来越多的证据表明泛素-蛋白酶体系统（UPS）至关重要，该系统能快速、有条不紊、彻底且单向地催化各种生物反应。UPS负责多种生物学上重要的细胞过程，如细胞周期进程、信号级联反应和发育程序。这个系统还参与蛋白质质量控制，维持细胞的稳态。特别值得关注的是，UPS为理解各种神经退行性疾病的分子机制提供了线索。在过去十年中，我们在揭示帕金森病（PD）的机制方面取得了巨大进展。在几个可导致家族性PD的基因中，常染色体隐性少年帕金森病（AR-JP）的致病基因parkin特别引人关注，因为它编码一种泛素蛋白连接酶，该酶将泛素共价连接到靶蛋白上，使其被蛋白酶体（一种真核生物依赖ATP的蛋白酶复合物）降解。本综述总结了近期关于UPS途径的研究，特别提及parkin，重点关注parkin如何与AR-JP的发病机制相关联。
