The ubiquitin ligase Fbxw7 controls adipocyte differentiation by targeting C/EBP alpha for degradation

作者：Bengoechea Alonso Maria T; Ericsson Johan^*

来源：Proceedings of the National Academy of Sciences, 2010, 107(26): 11817-11822.

DOI：10.1073/pnas.0913367107

• adipogenesis
• CCAAT/enhancer-binding protein

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 PPAR gamma and members of the C/EBP family of transcription factors. Here, we demonstrate that C/EBP alpha 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/EBP alpha. 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/EBP alpha 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/EBP alpha. Thus, Fbxw7 could be an important regulator of energy and lipid metabolism.

• 出版日期2010-6-29