Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor α interacting protein

Abstract

Nuclear receptor corepressor (NCoR) was demonstrated to interact strongly with peroxisome proliferator-activated receptor α (PPARα), and PPARα ligands suppressed this interaction. In contrast to the interaction of PPARα with the coactivator protein, p300, association of the receptor with NCoR did not require any part of the PPARα ligand binding domain. NCoR was found to suppress PPARα-dependent transcriptional activation in the context of a PPARα·retinoid X receptor α (RXRα) heterodimeric complex bound to a peroxisome proliferator-responsive element in human embryonic kidney 293 cells. This repression was reversed agonists of either receptor demonstrating a functional interaction between NCoR and PPARα·RXRα heterodimeric complexes in mammalian cells. NCoR appears to influence PPARα signaling pathways and, therefore, may modulate tissue responsiveness to peroxisome proliferators.