Send to

Choose Destination
PPAR Res. 2006;2006:69612.

Examination of Ligand-Dependent Coactivator Recruitment by Peroxisome Proliferator-Activated Receptor-alpha (PPARalpha).

Author information

Department of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, Pennsylvania State University, 201 Life Sciences Building, University Park, PA 16802, USA.


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.

Supplemental Content

Full text links

Icon for Hindawi Limited Icon for PubMed Central
Loading ...
Support Center