The role of the ubiquitin-proteasome system in kidney diseases.

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.