An oxysterol signalling pathway mediated by the nuclear receptor LXRα

B. A. Janowski, P. J. Willy, T. R. Devi, J R Falck, David J Mangelsdorf

Research output: Contribution to journalArticle

1283 Citations (Scopus)

Abstract

CHOLESTEROL and its oxysterol congeners are important constituents of cell membranes and function as intermediates in several crucial biosynthetic pathways. These compounds autoregulate their metabolic fate by end-product repression and activation of downstream catabolism. Although end-product repression by oxysterols is relatively well understood, the mechanism by which these compounds act as positive transcription signalling molecules is unknown. Here we identify a specific group of endogenous oxysterols that activate transcription through the nuclear receptor LXRα. Transactivation of LXRα by oxysterols occurs at concentrations at which these compounds exist in vivo. The most potent activators also serve as intermediary substrates in the rate-limiting steps of three important metabolic pathways: steroid hormone biosynthesis, bile acid synthesis, and conversion of lanosterol to cholesterol. Our results demonstrate the existence of a nuclear receptor signalling pathway for oxysterols and suggest that LXRα may be important as a sensor of cholesterol metabolites.

Original languageEnglish (US)
Pages (from-to)728-731
Number of pages4
JournalNature
Volume383
Issue number6602
DOIs
StatePublished - 1996

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Cytoplasmic and Nuclear Receptors
Cholesterol
Lanosterol
Biosynthetic Pathways
Metabolic Networks and Pathways
Bile Acids and Salts
Transcriptional Activation
Steroids
Cell Membrane
Oxysterols
Hormones

ASJC Scopus subject areas

  • General

Cite this

An oxysterol signalling pathway mediated by the nuclear receptor LXRα. / Janowski, B. A.; Willy, P. J.; Devi, T. R.; Falck, J R; Mangelsdorf, David J.

In: Nature, Vol. 383, No. 6602, 1996, p. 728-731.

Research output: Contribution to journalArticle

Janowski, B. A. ; Willy, P. J. ; Devi, T. R. ; Falck, J R ; Mangelsdorf, David J. / An oxysterol signalling pathway mediated by the nuclear receptor LXRα. In: Nature. 1996 ; Vol. 383, No. 6602. pp. 728-731.
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