title: Identification of a nuclear receptor that is activated by farnesol metabolites.
abstract: Nuclear hormone receptors comprise a superfamily of ligand-modulated transcription factors that mediate the transcriptional activities of steroids, retinoids, and thyroid hormones. A growing number of related proteins have been identified that possess the structural features of hormone receptors, but that lack known ligands. Known as orphan receptors, these proteins represent targets for novel signaling molecules. We have isolated a mammalian orphan receptor that forms a heterodimeric complex with the retinoid X receptor. A screen of candidate ligands identified farnesol and related metabolites as effective activators of this complex. Farnesol metabolites are generated intracellularly and are required for the synthesis of cholesterol, bile acids, steroids, retinoids, and farnesylated proteins. Intermediary metabolites have been recognized as transcriptional regulators in bacteria and yeast. Our results now suggest that metabolite-controlled intracellular signaling systems are utilized by higher organisms.
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Forman
authors.forename: E
authors.initials: E
authors.lastname: Goode
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: A E
authors.initials: AE
authors.lastname: Oro
authors.forename: D J
authors.initials: DJ
authors.lastname: Bradley
authors.forename: T
authors.initials: T
authors.lastname: Perlmann
authors.forename: D J
authors.initials: DJ
authors.lastname: Noonan
authors.forename: L T
authors.initials: LT
authors.lastname: Burka
authors.forename: T
authors.initials: T
authors.lastname: McMorris
authors.forename: W W
authors.initials: WW
authors.lastname: Lamph
authors.forename: R M
authors.initials: RM
authors.lastname: Evans
authors.forename: C
authors.initials: C
authors.lastname: Weinberger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005204:Farnesol / Q000031:analogs & derivatives / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D015398:Signal Transduction; D013729:Terpenes / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D004247:DNA; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005204:Farnesol; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013729:Terpenes; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated