Sterols and gene expression: Control of affluence

Kristina Schoonjans, Carole Brendel, David Mangelsdorf, Johan Auwerx

Research output: Contribution to journalReview article

37 Scopus citations

Abstract

Intracellular and extracellular cholesterol levels are tightly maintained within a narrow concentration range by an intricate transcriptional control mechanism. Excess cholesterol can be converted into oxysterols, signaling molecules, which modulate the activity of a number of transcription factors, as to limit accumulation of excess of cholesterol. Two key regulatory pathways are affected by oxysterols. The first pathway involves the uptake and de novo synthesis of cholesterol and is controlled by the family of sterol response element binding proteins, whose activity is regulated by a sterol-dependent feedback mechanism. The second pathway, which only recently has become a topic of interest, involves the activation by a feedforward mechanism of cholesterol utilization for either bile acid or steroid hormone synthesis by oxysterol-activated nuclear receptors, such as liver X receptor and steroidogenic factor-1. Furthermore, biosynthesis and enterohepatic reabsorption of bile acids are regulated by the farnesol X receptor, a receptor activated by bile acids. Both the feedback inhibition of cholesterol uptake and production and the stimulation of cholesterol utilization will ultimately result in a lowering of the intracellular cholesterol concentration and allow for a fine-tuned regulation of the cholesterol concentration. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)114-125
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1529
Issue number1-3
DOIs
StatePublished - Dec 15 2000

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Keywords

  • 9-cis retinoic acid receptor
  • Atherosclerosis
  • Cholesterol
  • Farnesol X receptor
  • Gene expression
  • Liver X receptor
  • Liver receptor homologue 1
  • Nuclear receptor
  • Oxysterol
  • Short heterodimeric partner
  • Steroidogenic factor-1
  • Sterol response element binding protein

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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