Identification of a nuclear receptor that is activated by farnesol metabolites

Cell. 1995 Jun 2;81(5):687-93. doi: 10.1016/0092-8674(95)90530-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Cells, Cultured
  • DNA / metabolism
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Farnesol / analogs & derivatives
  • Farnesol / metabolism*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Rats
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid / metabolism
  • Retinoid X Receptors
  • Signal Transduction*
  • Terpenes / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transfection


  • DNA, Complementary
  • DNA-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Terpenes
  • Transcription Factors
  • farnesoid X-activated receptor
  • Farnesol
  • DNA

Associated data

  • GENBANK/U18374