Title |
Transforming Growth Factor-β Inhibits Adipocyte Differentiation by Smad3 Interacting with CCAAT/Enhancer-binding Protein (C/EBP) and Repressing C/EBP Transactivation Function*
|
---|---|
Published in |
Journal of Biological Chemistry, January 2003
|
DOI | 10.1074/jbc.m212259200 |
Pubmed ID | |
Authors |
Lisa Choy, Rik Derynck |
Abstract |
Transforming growth factor (TGF)-beta is a potent inhibitor of adipocyte differentiation. To identify which adipocyte transcription factors might be targeted by TGF-beta, we overexpressed key adipogenic transcription factors, C/EBPbeta, C/EBPdelta, or peroxisome proliferator-activated receptor (PPAR) gamma in NIH3T3 cells and tested the ability of TGF-beta to block adipogenesis. We show that TGF-beta inhibits adipocyte differentiation driven by either C/EBPbeta or C/EBPdelta without affecting C/EBP protein expression levels, suggesting that these C/EBPs are a direct target of TGF-beta action. Because TGF-beta inhibits adipogenesis by signaling through Smad3, we examined physical and functional interactions of Smad3 and Smad4 with C/EBPbeta, C/EBPdelta, and PPARgamma2. C/EBPbeta and C/EBPdelta were found to physically interact with Smad3 and Smad4, and Smad3 cooperated with Smad4 and TGF-beta signaling to repress the transcriptional activity of C/EBPs. Thus, repression of the activity of C/EBPs by Smad3/4 at C/EBP binding sites inhibited transcription from the PPARgamma2 and leptin promoters. In contrast, PPARgamma interacted only very weakly with Smad3 and its transcriptional activity was not repressed by Smad3/4 or in response to TGF-beta. Smad3/4 did not reduce the ability of C/EBP to bind to its cognate DNA sequence, but repressed transcription by inhibiting the transactivation function of C/EBP. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 2% |
France | 1 | <1% |
Korea, Republic of | 1 | <1% |
Austria | 1 | <1% |
Japan | 1 | <1% |
Spain | 1 | <1% |
Unknown | 166 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 37 | 21% |
Student > Ph. D. Student | 31 | 18% |
Student > Bachelor | 18 | 10% |
Professor > Associate Professor | 16 | 9% |
Student > Postgraduate | 14 | 8% |
Other | 37 | 21% |
Unknown | 21 | 12% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 70 | 40% |
Biochemistry, Genetics and Molecular Biology | 40 | 23% |
Medicine and Dentistry | 16 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 5 | 3% |
Neuroscience | 3 | 2% |
Other | 8 | 5% |
Unknown | 32 | 18% |