title: Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation.
abstract: The role of the E3 ubiquitin ligase murine double minute 2 (Mdm2) in regulating the stability of the p53 tumor suppressor is well documented. By contrast, relatively little is known about p53-independent activities of Mdm2 and the role of Mdm2 in cellular differentiation. Here we report a novel role for Mdm2 in the initiation of adipocyte differentiation that is independent of its ability to regulate p53. We show that Mdm2 is required for cAMP-mediated induction of CCAAT/enhancer-binding protein δ (C/EBPδ) expression by facilitating recruitment of the cAMP regulatory element-binding protein (CREB) coactivator, CREB-regulated transcription coactivator (Crtc2)/TORC2, to the c/ebpδ promoter. Our findings reveal an unexpected role for Mdm2 in the regulation of CREB-dependent transactivation during the initiation of adipogenesis. As Mdm2 is able to promote adipogenesis in the myoblast cell line C2C12, it is conceivable that Mdm2 acts as a switch in cell fate determination.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Hallenborg
authors.forename: S
authors.initials: S
authors.lastname: Feddersen
authors.forename: S
authors.initials: S
authors.lastname: Francoz
authors.forename: I
authors.initials: I
authors.lastname: Murano
authors.forename: U
authors.initials: U
authors.lastname: Sundekilde
authors.forename: R K
authors.initials: RK
authors.lastname: Petersen
authors.forename: V
authors.initials: V
authors.lastname: Akimov
authors.forename: M V
authors.initials: MV
authors.lastname: Olson
authors.forename: G
authors.initials: G
authors.lastname: Lozano
authors.forename: S
authors.initials: S
authors.lastname: Cinti
authors.forename: B T
authors.initials: BT
authors.lastname: Gjertsen
authors.forename: L
authors.initials: L
authors.lastname: Madsen
authors.forename: J-C
authors.initials: JC
authors.lastname: Marine
authors.forename: B
authors.initials: B
authors.lastname: Blagoev
authors.forename: K
authors.initials: K
authors.lastname: Kristiansen
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D016159:Tumor Suppressor Protein p53; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2