title: Activation of extracellular signal-regulated kinases and CREB/ATF-1 mediate the expression of CCAAT/enhancer binding proteins beta and -delta in preadipocytes.
abstract: The essential role of CCAAT/enhancer binding proteins (C/EBPs) beta and delta for adipocyte differentiation has been clearly established. In preadipocytes, their expression is up-regulated by the activation of leukemia inhibitory factor receptor (LIF-R) and prostacyclin receptor (IP-R) via the extracellular signal-regulated kinase (ERK) pathway and cAMP production, respectively. However, the molecular mechanisms by which LIF and prostacyclin-induced signals are propagated to the nucleus and the transcription factors mediating ERK and cAMP-induced C/EBP gene expression were unknown. Here we report that both pathways share cAMP responsive element binding protein/activation transcription factor 1 (CREB/ATF-1) as common downstream effectors. LIF-R and IP-R activation induced binding of CREB and/or ATF-1 to C/EBP promoters and CREB-dependent transcription. Expression of dominant negative forms of CREB dramatically reduced the LIF- and prostacyclin-stimulated C/EBP beta and C/EBP delta expression. Upon stimulation of the IP-R, the ERK pathway was activated in a PKA-dependent manner. ERK activation by the PKA pathway was not required for CREB/ATF-1 phosphorylation but rather was necessary for CREB-dependent up-regulation of C/EBPs expression. Our findings suggest that ERK activation is required for CREB transcriptional activity, possibly by recruitment of a coactivator.
authors.affiliation: Institute of Signaling, Development Biology and Cancer Research, UMR 6543 Centre Nationale de la Recherche Scientifique, Centre de Biochimie 06108 Nice Cedex 2, France.
authors.forename: N
authors.initials: N
authors.lastname: Belmonte
authors.forename: B W
authors.initials: BW
authors.lastname: Phillips
authors.forename: F
authors.initials: F
authors.lastname: Massiera
authors.forename: P
authors.initials: P
authors.lastname: Villageois
authors.forename: B
authors.initials: B
authors.lastname: Wdziekonski
authors.forename: P
authors.initials: P
authors.lastname: Saint-Marc
authors.forename: J
authors.initials: J
authors.lastname: Nichols
authors.forename: J
authors.initials: J
authors.lastname: Aubert
authors.forename: K
authors.initials: K
authors.lastname: Saeki
authors.forename: A
authors.initials: A
authors.lastname: Yuo
authors.forename: S
authors.initials: S
authors.lastname: Narumiya
authors.forename: G
authors.initials: G
authors.lastname: Ailhaud
authors.forename: C
authors.initials: C
authors.lastname: Dani
mesh_terms: D051697:Activating Transcription Factor 1; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D011464:Epoprostenol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D018121:Receptors, Cytokine / Q000378:metabolism; D044006:Receptors, Epoprostenol; D053606:Receptors, OSM-LIF; D011982:Receptors, Prostaglandin / Q000819:agonists; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
chemical_list: D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497253:Cebpd protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507841:Lifr protein, mouse; D018121:Receptors, Cytokine; D044006:Receptors, Epoprostenol; D053606:Receptors, OSM-LIF; D011982:Receptors, Prostaglandin; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D011464:Epoprostenol; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases