USP7 Inhibits Osteoclastogenesis via Dual Effects of Attenuating TRAF6/TAK1 Axis and Stimulating STING Signaling.

ABSTRACT: Ubiquitination is a reversible post-translational modification implicated in cell differentiation, homeostasis, and organ development. Several deubiquitinases (DUBs) decrease protein ubiquitination through the hydrolysis of ubiquitin linkages. However, the role of DUBs in bone resorption and formation is still unclear. In this study, we identified DUB ubiquitin-specific protease 7 (USP7) as a negative regulator of osteoclast formation. USP7 combines with tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibits its ubiquitination by impairing the Lys63-linked polyubiquitin chain. Such impairment leads to the suppression of receptor activator of NF-κB ligand (RANKL)-mediated nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) activation without affecting TR

SUBMITTER: Xie Z 

PROVIDER: S-EPMC10676781 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature