Regulation of cholesterologenesis by the oxysterol receptor, LXRα

Yongjun Wang, Pamela M. Rogers, Chen Su, Gabor Varga, Keith R. Stayrook, Thomas P. Burris

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85 Scopus citations

Abstract

Cholesterol is required for normal cellular and physiological function, yet dysregulation of cholesterol metabolism is associated with diseases such as atherosclerosis. Cholesterol biosynthesis is regulated by end product negative feedback inhibition where the levels of sterols and oxysterols regulate the expression of cholesterologenic enzymes. Sterol regulatory element-binding protein-2 is responsive to both sterols and oxysterols and has been shown to mediate the transcriptional response of the cholesterologenic enzymes to these lipids. Here, we show that the nuclear hormone receptor for oxysterols, the liver X receptor α (LXRα), regulates cholesterol biosynthesis by directly silencing the expression of two key cholesterologenic enzymes (lanosterol 14α-demethylase (CYP51A1), and squalene synthase (farnesyl diphosphate farnesyl transferase 1)) via novel negative LXR DNA response elements (nLXREs) located in each of these genes. Examination of the CYP51A1 gene revealed that both the SRE and nLXRE are required for normal oxysterol-dependent repression of this gene. Thus, these data suggest that LXRα plays an important role in the regulation of cholesterol biosynthesis.

Original languageEnglish (US)
Pages (from-to)26332-26339
Number of pages8
JournalJournal of Biological Chemistry
Volume283
Issue number39
DOIs
StatePublished - Sep 26 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wang, Y., Rogers, P. M., Su, C., Varga, G., Stayrook, K. R., & Burris, T. P. (2008). Regulation of cholesterologenesis by the oxysterol receptor, LXRα. Journal of Biological Chemistry, 283(39), 26332-26339. https://doi.org/10.1074/jbc.M804808200