| First Author | Kilroy G | Year | 2012 |
| Journal | Endocrinology | Volume | 153 |
| Issue | 3 | Pages | 1206-18 |
| PubMed ID | 22294748 | Mgi Jnum | J:182529 |
| Mgi Id | MGI:5315805 | Doi | 10.1210/en.2011-1725 |
| Citation | Kilroy G, et al. (2012) The ubiquitin ligase Siah2 regulates PPARgamma activity in adipocytes. Endocrinology 153(3):1206-18 |
| abstractText | Moderate reductions in peroxisome proliferator-activated receptor (PPAR)gamma levels control insulin sensitivity as effectively as activation of PPARgamma in adipocytes by the thiazolidinediones. That observation suggests that PPARgamma activity can be regulated by modulating the amount of PPARgamma protein in adipocytes. Activation of PPARgamma in adipocytes is linked to changes in PPARgamma protein levels via increased degradation of PPARgamma proteins by the ubiquitin proteasome system. Identification of the ubiquitin ligase or ligases that recognize ligand bound PPARgamma is an essential step in determining the physiological significance of the relationship between activation and ubiquitin-dependent degradation of PPARgamma. Using an RNA interference-based screen, we identified five RING (really interesting new gene)-type ubiquitin ligases that alter PPARgamma protein levels in adipocytes. Here, we demonstrate that Drosophila seven-in-absentia homolog 2 (Siah2), a mammalian homolog of Drosophila seven-in-absentia, regulates PPARgamma ubiquitylation and ligand-dependent activation of PPARgamma in adipocytes. We also demonstrate that Siah2 expression is up-regulated during adipogenesis and that PPARgamma interacts with Siah2 during adipogenesis. In addition, Siah2 is required for adipogenesis. These data suggest that modulation of PPARgamma protein levels by the ubiquitin ligase Siah2 is essential in determining the physiological effects of PPARgamma activation in adipocytes. |
