| First Author | Yuzawa H | Year | 2009 |
| Journal | Bone | Volume | 44 |
| Issue | 1 | Pages | 53-60 |
| PubMed ID | 18950738 | Mgi Jnum | J:146021 |
| Mgi Id | MGI:3836518 | Doi | 10.1016/j.bone.2008.09.013 |
| Citation | Yuzawa H, et al. (2009) Arkadia represses the expression of myoblast differentiation markers through degradation of Ski and the Ski-bound Smad complex in C2C12 myoblasts. Bone 44(1):53-60 |
| abstractText | The differentiation of myoblasts is regulated by multiple extracellular and intracellular factors. Of the extracellular regulators, members of transforming growth factor-beta (TGF-beta) family play critical roles in the regulation of osteoblasts and myoblast differentiation. Little is known, however, about the regulation of Myostatin/TGF-beta signaling during myoblast differentiation. In this study, we examined the roles of Arkadia, an E3 ubiquitin ligase, in Myostatin/TGF-beta signaling and the regulation of myoblast differentiation. Knockdown of Arkadia reduced Myostatin/TGF-beta signaling and enhanced the differentiation of C2C12 myoblasts. In addition, exogenous overexpression of Arkadia enhanced Myostatin/TGF-beta signaling, preventing myoblast differentiation. In the absence of the activation of Myostatin/TGF-beta signaling, knockdown of Arkadia enhanced myoblast differentiation via upregulation of Ski protein, an intracellular enhancer of myoblast differentiation. Arkadia likely affected the differentiation of myoblasts in a Smad-independent fashion by inducing Ski degradation. Knockdown of Arkadia increased the Myostatin-induced phosphorylation of Smad2/3 in C2C12 cells. Arkadia bound Smad2/3 via Ski to induce the ubiquitination of Smad2/3. These results suggest that Arkadia targets Ski-bound, inactive phospho-Smad2/3 to regulate positively Myostatin/TGF-beta signaling. Taken together, this study indicates that Arkadia regulates myoblast differentiation through both Smad-dependent and Smad-independent pathways. |
