| First Author | Kim JH | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 8 | Pages | 5224-31 |
| PubMed ID | 20037154 | Mgi Jnum | J:159891 |
| Mgi Id | MGI:4452593 | Doi | 10.1074/jbc.M109.042812 |
| Citation | Kim JH, et al. (2010) Negative feedback control of osteoclast formation through ubiquitin-mediated down-regulation of NFATc1. J Biol Chem 285(8):5224-31 |
| abstractText | The regulation of NFATc1 expression is important for osteoclast differentiation and function. Herein, we demonstrate that macrophage-colony-stimulating factor induces NFATc1 degradation via Cbl proteins in a Src kinase-dependent manner. NFATc1 proteins are ubiquitinated and rapidly degraded during late stage osteoclastogenesis, and this degradation is mediated by Cbl-b and c-Cbl ubiquitin ligases in a Src-dependent manner. In addition, NFATc1 interacts endogenously with c-Src, c-Cbl, and Cbl-b in osteoclasts. Overexpression of c-Src induces down-regulation of NFATc1, and depletion of Cbl proteins blocks NFATc1 degradation during late stage osteoclastogenesis. Taken together, our data provide a negative regulatory mechanism by which macrophage-colony-stimulating factor activates Src family kinases and Cbl proteins, and subsequently, induces NFATc1 degradation during osteoclast differentiation. |
