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J Biol Chem, Vol. 274, Issue 12, 7681-7688, March 19, 1999

p300 Interacts with the N- and C-terminal Part of PPARgamma 2 in a Ligand-independent and -dependent Manner, Respectively

Laurent GelmanDagger , Gaochao Zhou, Lluis FajasDagger , Eric RaspéDagger , Jean-Charles FruchartDagger , and Johan AuwerxDagger

From the Dagger  Unité 325 INSERM, Département d'Athérosclérose, Institut Pasteur de Lille, 1, rue du Prof. Calmette, 59019 Lille Cédex, France and the  Merck Research Laboratories, Rahway, New Jersey 07065

The nuclear peroxisome proliferator-activated receptor gamma  (PPARgamma ) activates the transcription of multiple genes involved in intra- and extracellular lipid metabolism. Several cofactors are crucial for the stimulation or the silencing of nuclear receptor transcriptional activities. The two homologous cofactors p300 and CREB-binding protein (CBP) have been shown to co-activate the ligand-dependent transcriptional activities of several nuclear receptors as well as the ligand-independent transcriptional activity of the androgen receptor. We show here that the interaction between p300/CBP and PPARgamma is complex and involves multiple domains in each protein. p300/CBP not only bind in a ligand-dependent manner to the DEF region of PPARgamma but also bind directly in a ligand-independent manner to a region in the AB domain localized between residue 31 to 99. In transfection experiments, p300/CBP could thereby enhance the transcriptional activities of both the activating function (AF)-1 and AF-2 domains. p300/CBP displays itself at least two docking sites for PPARgamma located in its N terminus (between residues 1 and 113 for CBP) and in the middle of the protein (between residues 1099 and 1460).


Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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