The orphan nuclear hormone receptor LXRα interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome proliferator signaling

Abstract

The yeast two-hybrid system was used to isolate novel cellular factors that interact with the mouse peroxisome proliferator-activated receptor α (PPARα). One of the interacting clones isolated encoded LXRα, a recently described human orphan nuclear hormone receptor. LXRα bound directly to PPARα, as well as to the common heterodimerization partner 9-cis-retinoic acid receptor (RXRα). LXRα did not form a DNA binding complex with PPARα on synthetic hormone response elements composed of direct repeats of the TGACCT consensus half-site or on naturally occurring peroxisome proliferator response elements (PPREs) or LXRα response elements. However, LXRα inhibited binding of PPARα/RXRα heterodimers to PPREs, and coexpression of LXRα in mammalian cells antagonized peroxisome proliferator signaling mediated by PPARα/RXRα in vivo. These findings identify a novel partner for PPARα and suggest that LXRα plays a role in modulating PPAR-signaling pathways in the cell.