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

FEBS Lett. 2007 Jun 12;581(14):2715-20. doi: 10.1016/j.febslet.2007.05.022. Epub 2007 May 21.


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.

MeSH terms

  • Binding Sites / genetics
  • Blotting, Western
  • Cell Line, Tumor
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism*
  • Gene Expression / drug effects
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mutation
  • Promoter Regions, Genetic / genetics*
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Retinoid X Receptors / genetics
  • Retinoid X Receptors / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism*
  • Transfection
  • Tretinoin / pharmacology*


  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Recombinant Fusion Proteins
  • Retinoid X Receptors
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Tretinoin
  • Luciferases
  • Fatty Acid Synthases