LXR, a nuclear receptor that defines a distinct retinoid response pathway

P. J. Willy, K. Umesono, E. S. Ong, R. M. Evans, R. A. Heyman, D. J. Mangelsdorf

Research output: Contribution to journalArticle

800 Citations (Scopus)

Abstract

We have identified a new retinoid response pathway through which 9-cis retinoic acid (9cRA) activates transcription in the presence of LXRα, a member of the nuclear receptor superfamily. LXRα shows a specific pattern of expression in visceral organs, thereby restricting the response to certain tissues. Retinoid trans-activation occurs selectively on a distinct response element termed an LXRE. Significantly, neither RXR homodimers nor RXR/RAR heterodimers are able to substitute for LXRα in mediating this retinoid response. We provide evidence that the retinoid response on the LXRE is the result of a unique interaction between LXRα and endogenous RXR, which, unlike in the RXR/RAR heterodimer, makes RXR competent to respond to retinoids. Thus, the interaction with LXRα shifts RXR from its role described previously as a silent, DNA-binding partner to an active ligand- binding subunit in mediating retinoid responses through target genes defined by LXREs.

Original languageEnglish (US)
Pages (from-to)1033-1045
Number of pages13
JournalGenes and Development
Volume9
Issue number9
StatePublished - 1995

Fingerprint

Retinoids
Cytoplasmic and Nuclear Receptors
Response Elements
Ligands
DNA
Genes

Keywords

  • 9-cis retinoic acid
  • LXR
  • methoprene acid
  • orphan receptor
  • retinoid receptors
  • RXR

ASJC Scopus subject areas

  • Developmental Biology
  • Genetics

Cite this

Willy, P. J., Umesono, K., Ong, E. S., Evans, R. M., Heyman, R. A., & Mangelsdorf, D. J. (1995). LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes and Development, 9(9), 1033-1045.

LXR, a nuclear receptor that defines a distinct retinoid response pathway. / Willy, P. J.; Umesono, K.; Ong, E. S.; Evans, R. M.; Heyman, R. A.; Mangelsdorf, D. J.

In: Genes and Development, Vol. 9, No. 9, 1995, p. 1033-1045.

Research output: Contribution to journalArticle

Willy, PJ, Umesono, K, Ong, ES, Evans, RM, Heyman, RA & Mangelsdorf, DJ 1995, 'LXR, a nuclear receptor that defines a distinct retinoid response pathway', Genes and Development, vol. 9, no. 9, pp. 1033-1045.
Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes and Development. 1995;9(9):1033-1045.
Willy, P. J. ; Umesono, K. ; Ong, E. S. ; Evans, R. M. ; Heyman, R. A. ; Mangelsdorf, D. J. / LXR, a nuclear receptor that defines a distinct retinoid response pathway. In: Genes and Development. 1995 ; Vol. 9, No. 9. pp. 1033-1045.
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