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J. Biol. Chem., Vol. 278, Issue 38, 36959-36965, September 19, 2003

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CCAAT/Enhancer-binding Protein Family Members Recruit the Coactivator CREB-binding Protein and Trigger Its Phosphorylation^*

Krisztián A. Kovács  , Myriam Steinmann  , Pierre J. Magistretti  ¶, Olivier Halfon  and Jean-René Cardinaux   ||

From the Department of Child and Adolescent Psychiatry, the Center for Psychiatric Neuroscience, Department of Psychiatry, and the ^¶Institute of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland

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/EBP and C/EBP 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/EBP is also using CBP as a coactivator. Based on sequence homology with C/EBP and -, we identify in C/EBP 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/EBP. 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/EBP and define point mutations within one of the two conserved amino acid segments of C/EBP that abolish CBP phosphorylation as well as transcriptional activation, suggesting that this new mechanism could be important for C/EBP-mediated transcription.

Received for publication, March 27, 2003 , and in revised form, July 9, 2003.

^* This work was supported by a Fonds National Suisse de la Recherche Scientifique Grant 31-64031.00 (to J.-R. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Centre de Neurosciences Psychiatriques, 1er étage, Site de Cery, CH-1008 Prilly, Switzerland. Tel.: 41-21-643-6946; Fax: 41-21-643-6950; E-mail: Jean-Rene.Cardinaux{at}hospvd.ch.

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