title: CCAAT/enhancer-binding protein family members recruit the coactivator CREB-binding protein and trigger its phosphorylation.
abstract: CCAAT/enhancer-binding protein (C/EBP) family members are transcription factors involved in important physiological processes, such as cellular proliferation and differentiation, regulation of energy homeostasis, inflammation, and hematopoiesis. Transcriptional activation by C/EBPalpha and C/EBPbeta involves the coactivators CREB-binding protein (CBP) and p300, which promote transcription by acetylating histones and recruiting basal transcription factors. In this study, we show that C/EBPdelta is also using CBP as a coactivator. Based on sequence homology with C/EBPalpha and -beta, we identify in C/EBPdelta two conserved amino acid segments that are necessary for the physical interaction with CBP. Using reporter gene assays, we demonstrate that mutation of these residues prevents CBP recruitment and diminishes the transactivating potential of C/EBPdelta. In addition, our results indicate that C/EBP family members not only recruit CBP but specifically induce its phosphorylation. We provide evidence that CBP phosphorylation depends on its interaction with C/EBPdelta and define point mutations within one of the two conserved amino acid segments of C/EBPdelta that abolish CBP phosphorylation as well as transcriptional activation, suggesting that this new mechanism could be important for C/EBP-mediated transcription.
authors.affiliation: Department of Child and Adolescent Psychiatry, University of Lausanne, CH-1005 Lausanne, Switzerland.
authors.forename: Krisztián A
authors.initials: KA
authors.lastname: Kovács
authors.forename: Myriam
authors.initials: M
authors.lastname: Steinmann
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Magistretti
authors.forename: Olivier
authors.initials: O
authors.lastname: Halfon
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Cardinaux
mesh_terms: D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D050882:CREB-Binding Protein; D002455:Cell Division; D002460:Cell Line; D004926:Escherichia coli / Q000378:metabolism; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008156:Luciferases / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D051381:Rats; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; C497254:Cebpd protein, rat; D009687:Nuclear Proteins; D020033:Protein Isoforms; D015534:Trans-Activators; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D008156:Luciferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494365:Crebbp protein, rat; D005982:Glutathione Transferase