Genistein inhibits CCAAT/enhancer-binding protein beta (C/EBPbeta) activity and 3T3-L1 adipogenesis by increasing C/EBP homologous protein expression.

The tyrosine kinase inhibitor genistein inhibits 3T3-L1 adipogenesis when present during the first 72 h of differentiation. In this report, we investigated the underlying mechanisms involved in the anti-adipogenic effects of genistein. We found that genistein blocked the DNA binding and transcriptional activity of CCAAT/enhancer-binding protein beta (C/EBPbeta) during differentiation ...
by promoting the expression of C/EBP homologous protein, a dominant-negative member of the C/EBP family. Loss of C/EBPbeta activity was manifested as a loss of differentiation-induced C/EBPalpha and peroxisome-proliferator-activated receptor gamma protein expression and a dramatic reduction in lipid accumulation. Further, we documented for the first time that C/EBPbeta was tyrosine-phosphorylated in vivo during differentiation and in vitro by activated epidermal growth factor receptor. Genistein inhibited both of these events. Collectively, these results indicate that genistein blocks adipogenesis and C/EBPbeta activity by increasing the level of C/EBP homologous protein and possibly by inhibiting the tyrosine phosphorylation of C/EBPbeta.
Mesh Terms:
3T3 Cells, Adipocytes, Animals, Anticarcinogenic Agents, Azo Compounds, CCAAT-Enhancer-Binding Protein-beta, Cell Differentiation, Cell Line, Cell Nucleus, Coloring Agents, DNA, Enzyme Inhibitors, Genistein, Immunoblotting, Isoflavones, Lipid Metabolism, Mice, Phosphorylation, Precipitin Tests, Protein Binding, Receptors, Cytoplasmic and Nuclear, Time Factors, Transcription Factors, Transcription, Genetic, Transfection, Tyrosine
Biochem. J.
Date: Oct. 01, 2002
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