The Orphan Nuclear Hormone Receptor LXRα Interacts with the Peroxisome Proliferator-activated Receptor and Inhibits Peroxisome Proliferator Signaling (∗)

• Published in: The Journal of biological chemistry 1996-04, Vol.271 (16), p.9189-9192
• Main Authors: Miyata, Kenji S., McCaw, Shannon E., Patel, Hansa V., Rachubinski, Richard A., Capone, John P.
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding Sites; Cell Line; Cloning, Molecular; Consensus Sequence; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - isolation & purification; DNA-Binding Proteins - metabolism; Humans; Liver X Receptors; Macromolecular Substances; Mice; Microbodies - drug effects; Microbodies - physiology; Molecular Sequence Data; Oligodeoxyribonucleotides; Orphan Nuclear Receptors; Protein Biosynthesis; Receptors, Cytoplasmic and Nuclear - biosynthesis; Receptors, Cytoplasmic and Nuclear - isolation & purification; Receptors, Cytoplasmic and Nuclear - physiology; Receptors, Retinoic Acid - biosynthesis; Receptors, Retinoic Acid - isolation & purification; Receptors, Retinoic Acid - metabolism; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - isolation & purification; Recombinant Fusion Proteins - metabolism; Repetitive Sequences, Nucleic Acid; Retinoid X Receptors; Signal Transduction; Transcription Factors - biosynthesis; Transcription Factors - isolation & purification; Transcription Factors - metabolism; Transcription Factors - physiology; Transcription, Genetic; Tretinoin - metabolism; Tretinoin - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.16.9189

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.