Renal Division, Department of Internal Medicine, Iwata City Hospital, 512-3 Ohkubo, Iwata, Shizuoka 438-8550, Japan.
Clin Exp Nephrol. 2012 Aug;16(4):507-17. doi: 10.1007/s10157-012-0643-1. Epub 2012 Jun 9.
Proteins in mammalian cells are continually being degraded and synthesized. Protein degradation via the ubiquitin-proteasome system (UPS) is the major pathway for non-lysosomal proteolysis of intracellular proteins and plays important roles in a variety of fundamental cellular processes such as regulation of cell cycle progression, differentiation, apoptosis, sodium channel function, and modulation of inflammatory responses. The central element of this system is the covalent linkage of ubiquitins to targeted proteins, which are then recognized by the 26S proteasome composed of adenosine triphosphate-dependent, multi-catalytic proteases. Damaged or misfolded proteins, as well as regulatory proteins that control many critical cellular functions, are among the targets of this degradation process. Consequently, aberration of the system leads to dysregulation of cellular homeostasis and development of many diseases. Based on the findings, it is not surprising that abnormalities of the system are also associated with the pathogenesis of kidney diseases. In this review, I discuss (1) the basic mechanism of the UPS, and (2) the association between the pathogenesis of kidney diseases and the UPS. Diverse roles of the UPS are implicated in the development of kidney diseases, and further studies on this system may reveal new strategies for overcoming kidney diseases.
哺乳动物细胞中的蛋白质不断被降解和合成。通过泛素-蛋白酶体系统 (UPS) 进行的蛋白质降解是细胞内蛋白质非溶酶体降解的主要途径，在多种基本细胞过程中发挥重要作用，如细胞周期进程、分化、凋亡、钠通道功能和炎症反应的调节。该系统的核心要素是泛素与靶向蛋白的共价连接，然后被由三磷酸腺苷依赖性多催化蛋白酶组成的 26S 蛋白酶体识别。受损或错误折叠的蛋白质以及控制许多关键细胞功能的调节蛋白都是这种降解过程的目标。因此，该系统的异常会导致细胞内稳态失调和许多疾病的发生。基于这些发现，该系统的异常与肾脏疾病的发病机制也有关联并不奇怪。在这篇综述中，我讨论了 (1) UPS 的基本机制，以及 (2) 肾脏疾病发病机制与 UPS 之间的关系。UPS 的多种作用与肾脏疾病的发展有关，对该系统的进一步研究可能会揭示克服肾脏疾病的新策略。
