p300 interacts with the N- and C-terminal part of PPAR gamma 2 in a ligand-independent and -dependent manner, respectively

Citation
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
Citations number
48
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
274
Issue
12
Year of publication
1999
Pages
7681 - 7688
Database
ISI
SICI code
0021-9258(19990319)274:12<7681:PIWTNA>2.0.ZU;2-L
Abstract
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).