Regulation of adipogenesis by a transcriptional repressor that modulates MAPK activation

Mitogen-activated protein kinase (MAPK) is required for cell growth and cel l differentiation. In adipogenesis, MAPK activation opposes the differentia tion process. The regulatory mechanisms or the cellular factors that regula te the switch between growth and differentiation in the adipogenic lineage have been largely unelucidated. We show here that AEBP1, a transcriptional repressor that is down-regulated during adipogenesis, complexes and protect s MAPK from its specific phosphatase in mammalian cells. We further show ev idence that the modulation of MAPK activation by AEBP1 is a biologically re levant process in adipogenesis. Our results suggest that modulation of MAPK activation by the protective effect of AEBP1 may constitute a critical par t in the determination between cell growth and differentiation in the adipo genic lineage. The proposed mode of action by which a transcription factor regulates MAPK activation is novel.