| First Author | Bengoechea-Alonso MT | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 26 | Pages | 11817-22 |
| PubMed ID | 20534483 | Mgi Jnum | J:161392 |
| Mgi Id | MGI:4458975 | Doi | 10.1073/pnas.0913367107 |
| Citation | Bengoechea-Alonso MT, et al. (2010) The ubiquitin ligase Fbxw7 controls adipocyte differentiation by targeting C/EBP{alpha} for degradation. Proc Natl Acad Sci U S A 107(26):11817-22 |
| abstractText | Adipose tissue controls body lipid and energy metabolism, as well as food intake, and abnormalities in adipose function play a central role in diseases such as obesity and type-2 diabetes. Adipocyte differentiation is controlled by a transcriptional cascade involving PPARgamma and members of the C/EBP family of transcription factors. Here, we demonstrate that C/EBPalpha is targeted for degradation by the ubiquitin ligase Fbxw7 in a phosphorylation-dependent manner. Importantly, inactivation of Fbxw7 is sufficient to convert mouse preadipocytes into mature adipocytes in a manner dependent on C/EBPalpha. In addition, inactivation of Fbxw7 promotes adipocyte differentiation of human adult stem cells. Taken together, our results suggest that Fbxw7 is a negative regulator of adipogenesis by targeting C/EBPalpha for degradation. This notion is supported by the observation that the expression of Fbxw7 is down-regulated during adipocyte differentiation, resulting in the accumulation of proadipogenic proteins such as C/EBPalpha. Thus, Fbxw7 could be an important regulator of energy and lipid metabolism. |
