Ubiquitin-specific protease 3 targets TRAF6 for deubiquitination and suppresses IL-1β induced chondrocyte apoptosis.

Abstract

Traditionally, the development of osteoarthritis (OA) is associated with factors such as aging and injure, but more and more epidemiological and biological evidence suggests that the disease is closely related to metabolic syndrome and metabolic components. Ubiquitin-specific protease 3(USP3), a member of the USPs family, is a specific protease capable of cleavage of ubiquitin chains linked by proline residues. In our presented study, we firstly found that USP3 expression level was decreased in OA. USP3 overexpression inhibited IL-1β induced chondrocytes apoptosis and nuclear factor κB (NF-κB) activation. USP3 knockdown induced chondrocytes apoptosis and activated NF-κB pathway. USP3 interacts with TRAF6 (tumor necrosis factor-receptor-associated factor 6), which is an essential adaptor protein for the NF-κB (nuclear factor κB) signaling pathway and plays important roles in inflammation and immune response. IL-1β treatment up-regulated the polyubiquitination of TRAF6 in chondrocytes, which was attenuated when USP3 was forced expression. Our study mechanistically links USP3 to TRAF6 in osteoarthritis development. Moreover, these data support the pursuit of USP3 and TRAF6 as potential targets for osteoarthritis therapies.

• Authors: Qi Zhou, Zhonghua Xiao, Rong Zhou, Yiqin Zhou, Peiliang Fu, Xiang Li, Yuli Wu, Haishan Wu, Qirong Qian
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 514 Issue 2 Pg. 482-489 (06 25 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 31056254 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• IL1B protein, human
• Interleukin-1beta
• Intracellular Signaling Peptides and Proteins
• NF-kappa B
• Tifab protein, human
• Ubiquitin
• Deubiquitinating Enzymes
• USP3 protein, human
• Ubiquitin-Specific Proteases

Topics

• Apoptosis
• Cells, Cultured
• Chondrocytes (cytology, pathology)
• Deubiquitinating Enzymes (metabolism)
• Humans
• Interleukin-1beta (metabolism)
• Intracellular Signaling Peptides and Proteins (metabolism)
• NF-kappa B (metabolism)
• Osteoarthritis (drug therapy, enzymology, metabolism, pathology)
• Ubiquitin (metabolism)
• Ubiquitin-Specific Proteases (metabolism)
• Ubiquitination