期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 26, 页码 11817-11822出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0913367107
关键词
adipogenesis; CCAAT/enhancer-binding protein
资金
- Ludwig Institute for Cancer Research Ltd
- Science Foundation Ireland [07/SK/B1242b]
- Science Foundation Ireland (SFI) [07/SK/B1242b] Funding Source: Science Foundation Ireland (SFI)
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.
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