Clinical and Experimental Nephrology

, Volume 16, Issue 4, pp 507–517 | Cite as

The role of the ubiquitin–proteasome system in kidney diseases

Review Article


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.


Protein degradation Ubiquitin 26S proteasome E3 ligase 



Acute kidney injury


Activin-like kinase-5


Adenosine monophosphate


Adenosine triphosphate


CREB-binding protein


cAMP response element binding protein


Chronic kidney disease


cdc kinase subunit 1


Extracellular matrix


Epithelial-mesenchymal transition




Epithelial sodium channel


Ectopic viral integration site-1


Forkhead box O


Glomerular basement membrane


Homologous to E6-AP C-terminus


Hypoxia-inducible factor-α


Insulin-like growth factor-I


Inhibitor кB


Low-density lipoprotein


Muscle atrophy F-box


Melanocyte-specific gene 1


Muscle ring finger 1


Neural precursor cell-expressed developmentally downregulated 4


Nuclear factor-кB




Phosphatidylinositol 3-kinase


Peroxisome proliferator-activated receptor-γ


Really interesting new gene


Smad anchor for receptor activation




Serum- and glucocorticoid-inducible protein kinase 1


Sloan-Kettering Institute proto-oncogene


S-phase kinase-associated protein 2


Smad-ubiquitination regulatory factor 1


ski-related novel gene N


TGF-β type I receptor


TGF-β type II receptor


TGF-β receptors


Transforming growth factor-β


Tumor necrosis factor


Ubiquitin–proteasome system


Unilateral ureteral obstruction


von Hippel–Lindau protein


von Hippel–Lindau disease


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Copyright information

© Japanese Society of Nephrology 2012

Authors and Affiliations

  1. 1.Renal Division, Department of Internal MedicineIwata City HospitalIwataJapan

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