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

Nuclear receptor corepressor (NCoR) was demonstrated to interact strongly with peroxisome proliferator-activated receptor alpha (PPAR alpha), and PPAR alpha ligands suppressed this interaction. In contrast to the interaction of PPAR alpha with the coactivator protein, p300, association of the receptor with NCoR did not require any part of the PPAR alpha ligand binding domain. NCoR was found to suppress PPAR alpha-dependent transcriptional activation in the context of a PPAR alpha.retinoid X receptor alpha (RXR alpha) 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 PPAR alpha.RXR alpha heterodimeric complexes in mammalian cells. NCoR appears to influence PPARa signaling pathways and, therefore, may modulate tissue responsiveness to peroxisome proliferators.