Hershko A, Ciechanover A
Unit of Biochemistry, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Annu Rev Biochem. 1998;67:425-79. doi: 10.1146/annurev.biochem.67.1.425.
The selective degradation of many short-lived proteins in eukaryotic cells is carried out by the ubiquitin system. In this pathway, proteins are targeted for degradation by covalent ligation to ubiquitin, a highly conserved small protein. Ubiquitin-mediated degradation of regulatory proteins plays important roles in the control of numerous processes, including cell-cycle progression, signal transduction, transcriptional regulation, receptor down-regulation, and endocytosis. The ubiquitin system has been implicated in the immune response, development, and programmed cell death. Abnormalities in ubiquitin-mediated processes have been shown to cause pathological conditions, including malignant transformation. In this review we discuss recent information on functions and mechanisms of the ubiquitin system. Since the selectivity of protein degradation is determined mainly at the stage of ligation to ubiquitin, special attention is focused on what we know, and would like to know, about the mode of action of ubiquitin-protein ligation systems and about signals in proteins recognized by these systems.
真核细胞中许多短命蛋白质的选择性降解是由泛素系统完成的。在这条途径中，蛋白质通过与泛素（一种高度保守的小蛋白质）共价连接而被靶向降解。泛素介导的调节蛋白降解在众多过程的控制中发挥着重要作用，包括细胞周期进程、信号转导、转录调控、受体下调和内吞作用。泛素系统与免疫反应、发育和程序性细胞死亡有关。泛素介导过程中的异常已被证明会导致包括恶性转化在内的病理状况。在这篇综述中，我们讨论了关于泛素系统功能和机制的最新信息。由于蛋白质降解的选择性主要在与泛素连接的阶段决定，因此特别关注我们所知道的以及想要知道的关于泛素 - 蛋白质连接系统的作用方式和这些系统识别的蛋白质中的信号。
