The Ubiquitin-Proteasome System and Its Role in Inflammatory and Autoimmune Diseases

• Published in: Cellular & molecular immunology Vol. 3; no. 4; pp. 255 - 261
• Main Authors: Wang, Jingsong, Maldonado, Michael A
• Format: Journal Article
• Language: English
• Published: China Translational Medicine, Wyeth Research, Collegeville, PA 19426, USA%Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA 01.08.2006
• Subjects: Animals; Autoimmune Diseases - etiology; Autoimmune Diseases - metabolism; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Humans; Inflammation - etiology; Proteasome Endopeptidase Complex - physiology; Proteasome Inhibitors; Ubiquitin - physiology; 免疫疾病; 泛激素; proteasome; inflammation; autoimmune disease; ubiquitin; protein degradation
• ISSN: 1672-7681; 2042-0226

Protein degradation through the ubiquitin-proteasome system is the major pathway of non-lysosomal proteolysis of intracellular proteins. It plays important roles in a variety of fundamental cellular processes such as regulation of cell cycle progression, division, development and differentiation, apoptosis, cell trafficking, and modulation of the immune and inflammatory responses. The central element of this system is the covalent linkage of ubiquitin to targeted proteins, which are then recognized by the 26S proteasome, an adenosine triphosphate-dependent, multi-catalytic protease. Damaged, oxidized, or misfolded proteins as well as regulatory proteins that control many critical cellular functions are among the targets of this degradation process. Aberration of this system leads to the dysregulation of cellular homeostasis and the development of multiple diseases. In this review, we described the basic biochemistry and molecular biology of the ubiquitin-proteasome system, and its complex role in the development of inflammatory and autoimmune diseases. In addition, therapies and potential therapeutic targets related to the ubiquitin-proteasome system are discussed as well.