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SREBP-1c mediates the retinoid-dependent increase in fatty acid synthase promoter activity in HepG2

Roder, Karim, Zhang, Lei and Schweizer, Michael 2007. SREBP-1c mediates the retinoid-dependent increase in fatty acid synthase promoter activity in HepG2. FEBS Letters 581 (14) , pp. 2715-2720. 10.1016/j.febslet.2007.05.022

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Abstract

Treatment of HepG2 with all-trans retinoic acid (RA) induces expression of fatty acid synthase (FAS) mRNA and protein. Transfections show that the FAS promoter positively responds to retinoid X receptor (RXR) but not to RA receptor (RAR) agonists. Since RXR alone is capable of mediating the RA response of FAS, the existence of a classical RA-responsive element in the FAS promoter may be ruled out. Binding sites for NF-Y and SREBP-1 proved to be essential for the RA response. Exposure to all-trans RA increased mRNA and protein levels of SREBP-1, a transcriptional activator for FAS. Overexpression of a dominant-negative form of SREBP-1c diminished the RA-dependent increase in promoter activity. These data demonstrate that RXR ligands can stimulate the expression of a lipogenic gene solely by inducing transcription and cleavage of membrane-bound SREBP-1c.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 0014-5793
Date of First Compliant Deposit: 27 June 2017
Last Modified: 11 Dec 2017 12:36
URI: http://orca-mwe.cf.ac.uk/id/eprint/101770

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