L. Gelman et al., p300 interacts with the N- and C-terminal part of PPAR gamma 2 in a ligand-independent and -dependent manner, respectively, J BIOL CHEM, 274(12), 1999, pp. 7681-7688
The nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) a
ctivates the transcription of multiple genes involved in intra- and extrace
llular lipid metabolism. Several cofactors are crucial for the stimulation
or the silencing of nuclear receptor transcriptional activities. The two ho
mologous cofactors p300 and CREB-binding protein (CBP) have been shown to c
o-activate the ligand-dependent transcriptional activities of several nucle
ar receptors as well as the ligand-independent transcriptional activity of
the androgen receptor. We show here that the interaction between p300/CBP a
nd PPAR gamma is complex and involves multiple domains in each protein, p30
0/CBP not only bind in a ligand-dependent manner to the DEF region of PPAR
gamma but also bind directly in a ligand-independent manner to a region in
the AB domain localized between residue 31 to 99, In transfection experimen
ts, p300/CBP could thereby enhance the transcriptional activities of both t
he activating function (AF)-1 and AF-2 domains. p300/CBP displays itself at
least two docking sites for PPAR gamma located in its N terminus (between
residues 1 and 113 for CBP) and in the middle of the protein (between resid
ues 1099 and 1460).