Oleate Potentiates Oxysterol Inhibition of Transcription From Sterol Regulatory Element-1-Regulated Promoters and Maturation of Sterol Regulatory Element-Binding Proteins

Creator(s)

Douglas P. Thewke, Quillen-Dishner College of MedicineFollow
Sankhavaram R. Panini, Quillen-Dishner College of Medicine
Michael Sinensky, Quillen-Dishner College of Medicine

Document Type

Article

Publication Date

8-14-1998

Description

Activation of genes containing SRE-1 (sterol regulatory element 1) sequences is known to be under the regulation of sterols through modulation of the proteolytic maturation of SREBPs (SRE-1-binding proteins). Previous work has demonstrated SREBP-mediated transcriptional activation of genes encoding enzymes of sterol and fatty acid biosynthesis. Because synthesis of both sterols and C18 fatty acids are required for cell growth, in the absence of exogenous supplements of these lipids, we examined the hypothesis that fatty acid can also be regulatory in SREBP maturation. Our data indicate that C18 fatty acids can potentiate the biological activities of a typical, regulatory sterol: 25-hydroxycholesterol. Inhibition of C18 fatty acid synthesis in cells cultured in serum-free medium renders them resistant to killing by 25-hydroxycholesterol. Repression of expression of reporter constructs driven by promoters bearing SRE-1 element(s) by 25- hydroxycholesterol is increased by C18 fatty acid supplementation. C18 fatty acids also increase the inhibitory effect of 25-hydroxycholesterol on proteolytic maturation and nuclear localization of SREBPs. Furthermore, we also show that C18 fatty acid supplementation can enhance the inhibitory effect of 25-hydroxycholesterol on sterol and fatty acid biosynthesis. These results demonstrate that maximal down-regulation of SREBP maturation and the consequent repression of SRE-1 promoters occurs in response to both a regulatory sterol and fatty acid.

Copyright Statement

© 1998 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Citation Information

Thewke, Douglas P.; Panini, Sankhavaram R.; and Sinensky, Michael. 1998. Oleate Potentiates Oxysterol Inhibition of Transcription From Sterol Regulatory Element-1-Regulated Promoters and Maturation of Sterol Regulatory Element-Binding Proteins. Journal of Biological Chemistry. Vol.273(33). 21402-21407. https://doi.org/10.1074/jbc.273.33.21402 PMID: 9694903 ISSN: 0021-9258