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SREBP‐1c mediates the retinoid‐dependent increase in fatty acid synthase promoter activity in HepG2
Author(s) -
Roder Karim,
Zhang Lei,
Schweizer Michael
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.05.022
Subject(s) - fatty acid synthase , retinoic acid , retinoid x receptor , sterol regulatory element binding protein , activator (genetics) , retinoid , transcription (linguistics) , response element , receptor , messenger rna , promoter , biology , retinoic acid receptor , chemistry , transcription factor , microbiology and biotechnology , gene expression , enzyme , gene , biochemistry , nuclear receptor , philosophy , linguistics
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.