Ubiquitin C-terminal hydrolase-L3 regulates Smad1 ubiquitination and osteoblast differentiation

Abstract

Ubiquitin C-terminal hydrolase-L3 (Uch-L3), a deubiquitinating enzyme, is upregulated in bone morphogenetic protein 2-induced osteoblast differentiation. The mechanism and role of Uch-L3 in the process of osteoblast differentiation is unknown. We found that Uch-L3 physically interacts with Smad1 and dramatically decreases the amount of poly-ubiquitinated Smad1. Osteoblast differentiation was enhanced in the C2C12 cells stably transfected with Uch-L3. Otherwise, the siRNA knock-down of Uch-L3 resulted in the decrease of osteoblast differentiation. These results suggest that Uch-L3 enhances osteoblast differentiation through the stabilization of Smad1 signaling. Thus, Uch-L3 acts to fine-tune the process of Smad1 activation.Structured summary of protein interactionsUCHL3 physically interacts with SMAD1 by anti tag coimmunoprecipitation (View interaction)UCHL3 physically interacts with SMAD1 by anti bait coimmunoprecipitation (View interaction)SMAD1 physically interacts with UCHL3 by anti tag coimmunoprecipitation (View interaction)UCHL3 physically interacts with SMAD1 by anti tag coimmunoprecipitation (View interaction