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J Biol Chem, Vol. 274, Issue 12, 7681-7688, March 19, 1999
2 in a
Ligand-independent and -dependent Manner, Respectively
,
,
,
, and
From the The nuclear peroxisome proliferator-activated
receptor
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
(PPAR
) 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 PPAR
is complex and involves multiple domains
in each protein. p300/CBP not only bind in a
ligand-dependent manner to the DEF region of PPAR
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 PPAR
located in its N terminus
(between residues 1 and 113 for CBP) and in the middle of the protein
(between residues 1099 and 1460).
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