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

822 Scopus citations

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
DOIs
StatePublished - May 1 1995

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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