Sterols regulate 3β-hydroxysterol Δ24-reductase (DHCR24) via dual sterol regulatory elements: Cooperative induction of key enzymes in lipid synthesis by Sterol Regulatory Element Binding Proteins
| Autor: | Laura J. Sharpe, Andrew J. Brown, Eser J. Zerenturk |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Oxidoreductases Acting on CH-CH Group Donors
Farnesyltransferase Molecular Sequence Data Nerve Tissue Proteins CHO Cells Reductase Gene Expression Regulation Enzymologic Cricetulus Cricetinae polycyclic compounds Animals Promoter Regions Genetic Liver X receptor Molecular Biology Transcription factor Liver X Receptors Regulation of gene expression Binding Sites Base Sequence biology Cell Biology Orphan Nuclear Receptors Lipids Sterol Sterol regulatory element-binding protein Sterols Farnesyl-Diphosphate Farnesyltransferase CCAAT-Binding Factor Receptors LDL Biochemistry LDL receptor biology.protein lipids (amino acids peptides and proteins) Sterol Regulatory Element Binding Protein 2 |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1821:1350-1360 |
| ISSN: | 1388-1981 |
| Popis: | 3β-Hydroxysterol Δ24-reductase (DHCR24) catalyzes a final step in cholesterol synthesis, and has been ascribed diverse functions, such as being anti-apoptotic and anti-inflammatory. How this enzyme is regulated transcriptionally by sterols is currently unclear. Some studies have suggested that its expression is regulated by Sterol Regulatory Element Binding Proteins (SREBPs) while another suggests it is through the Liver X Receptor (LXR). However, these transcription factors have opposing effects on cellular sterol levels, so it is likely that one predominates. Here we establish that sterol regulation of DHCR24 occurs predominantly through SREBP-2, and identify the particular region of the DHCR24 promoter to which SREBP-2 binds. We demonstrate that sterol regulation is mediated by two sterol regulatory elements (SREs) in the promoter of the gene, assisted by two nearby NF-Y binding sites. Moreover, we present evidence that the dual SREs work cooperatively to regulate DHCR24 expression by comparison to two known SREBP target genes, the LDL receptor with one SRE, and farnesyl-diphosphate farnesyltransferase 1, with two SREs. |
| Databáze: | OpenAIRE |
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