The ubiquitin ligase Fbxw7 controls adipocyte differentiation by targeting C/EBPalpha for degradation.
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.
Mesh Terms:
3T3-L1 Cells, Adipocytes, Adipogenesis, Adult, Adult Stem Cells, Animals, CCAAT-Enhancer-Binding Protein-alpha, Cell Cycle Proteins, Cell Differentiation, F-Box Proteins, Humans, Mice, Models, Biological, NIH 3T3 Cells, RNA, Small Interfering, Substrate Specificity, Ubiquitin-Protein Ligases
3T3-L1 Cells, Adipocytes, Adipogenesis, Adult, Adult Stem Cells, Animals, CCAAT-Enhancer-Binding Protein-alpha, Cell Cycle Proteins, Cell Differentiation, F-Box Proteins, Humans, Mice, Models, Biological, NIH 3T3 Cells, RNA, Small Interfering, Substrate Specificity, Ubiquitin-Protein Ligases
Proc. Natl. Acad. Sci. U.S.A.
Date: Jun. 29, 2010
PubMed ID: 20534483
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