Examination of Ligand-Dependent Coactivator Recruitment by Peroxisome Proliferator-Activated Receptor-alpha (PPARalpha).
PPAR Res
; 2006: 69612, 2006.
Article
en En
| MEDLINE
| ID: mdl-17259669
The ligand-dependent recruitment of coactivators to peroxisome proliferator-activated receptor-alpha (PPARalpha) was examined. PPAR-binding protein (PBP), PPARgamma coactivator-1alpha (PGC-1alpha), steroid receptor coactivator-1 (SRC-1), and CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2) affected PPARalpha activity in the presence of Wy-14,643. The effects on PPARalpha activity in light of increased or decreased expression of these coactivators were qualitatively different depending on the ligand examined. Diminished expression of PGC-1alpha, SRC-1, or PBP by RNAi plasmids affected natural or synthetic agonist activity whereas only Wy-14,643 was affected by decreased PGC-1alpha. The interaction of PPARalpha with an LXXLL-containing peptide library showed ligand-specific patterns, indicative of differences in conformational change. The association of coactivators to PPARalpha occurs predominantly via the carboxyl-terminus and mutating (456)LHPLL to (456)LHPAA resulted in a dominant-negative construct. This research confirms that coactivator recruitment to PPARalpha is ligand-dependent and that selective receptor modulators (SRMs) of this important protein are likely.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
PPAR Res
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos