The orphan nuclear hormone receptor LXR alpha interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome proliferator signaling.
The yeast two-hybrid system was used to isolate novel cellular factors that interact with the mouse peroxisome proliferator-activated receptor alpha (PPARalpha). One of the interacting clones isolated encoded LXRalpha, a recently described human orphan nuclear hormone receptor. LXRalpha bound directly to PPARalpha, as well as to the common heterodimerization partner 9-cis-retinoic acid receptor (RXRalpha). LXRalpha did not form a DNA binding complex with PPARalpha 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 LXRalpha response elements. However, LXRalpha inhibited binding of PPARalpha/RXRalpha heterodimers to PPREs, and coexpression of LXRalpha in mammalian cells antagonized peroxisome proliferator signaling mediated by PPARalpha/RXRalpha in vivo. These findings identify a novel partner for PPARalpha and suggest that LXRalpha plays a role in modulating PPAR-signaling pathways in the cell.
Miyata
K S
KS
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
McCaw
S E
SE
Patel
H V
HV
Rachubinski
R A
RA
Capone
J P
JP
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D000071518:Liver X Receptors; D046911:Macromolecular Substances; D051379:Mice; D008830:Microbodies / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D057093:Orphan Nuclear Receptors; D014176:Protein Biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D046911:Macromolecular Substances; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D009838:Oligodeoxyribonucleotides; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin