Regulation of adipogenesis by a transcriptional repressor that modulates MAPK activation.
Mitogen-activated protein kinase (MAPK) is required for cell growth and cell differentiation. In adipogenesis, MAPK activation opposes the differentiation process. The regulatory mechanisms or the cellular factors that regulate 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 protects MAPK from its specific phosphatase in mammalian cells. We further show evidence that the modulation of MAPK activation by AEBP1 is a biologically relevant process in adipogenesis. Our results suggest that modulation of MAPK activation by the protective effect of AEBP1 may constitute a critical part in the determination between cell growth and differentiation in the adipogenic lineage. The proposed mode of action by which a transcription factor regulates MAPK activation is novel.
Kim
S W
SW
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Sir Charles Tupper Medical Bldg., Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada.
Muise
A M
AM
Lyons
P J
PJ
Ro
H S
HS
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation; D005799:Genes, Dominant; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008957:Models, Genetic; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; D015500:Chloramphenicol O-Acetyltransferase; D020928:Mitogen-Activated Protein Kinases; D010744:Phosphoric Monoester Hydrolases