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- Title
Examination of Ligand-Dependent Coactivator Recruitment by Peroxisome Proliferator-Activated Receptor-α (PPARα).
- Authors
Tien, Eric S.; Hannon, Daniel S.; Thompson, Jerry T.; Vanden Heuvel, John P.
- Abstract
The ligand-dependent recruitment of coactivators to peroxisome proliferator-activated receptor-α (PPARα) was examined. PPARbinding protein (PBP), PPARγ coactivator-1α (PGC-1α), steroid receptor coactivator-1 (SRC-1), and CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2) affected PPARα activity in the presence of Wy-14,643. The effects on PPARα activity in light of increased or decreased expression of these coactivators were qualitatively different depending on the ligand examined. Diminished expression of PGC-1α, SRC-1, or PBP by RNAi plasmids affected natural or synthetic agonist activity whereas only Wy-14,643 was affected by decreased PGC-1α. The interaction of PPARα with an LXXLL-containing peptide library showed ligand-specific patterns, indicative of differences in conformational change. The association of coactivators to PPARα occurs predominantly via the carboxyl-terminus and mutating 456LHPLL to 456LHPAA resulted in a dominant-negative construct. This research confirms that coactivator recruitment to PPARα is ligand-dependent and that selective receptor modulators (SRMs) of this important protein are likely.
- Subjects
CELL receptors; RECEPTOR-ligand complexes; PEROXISOMES; CARRIER proteins; LIGANDS (Biochemistry)
- Publication
PPAR Research, 2006, p1
- ISSN
1687-4757
- Publication type
Article
- DOI
10.1155/PPAR/2006/69612