title: Resveratrol stimulates AP-1-regulated gene transcription.
abstract: METHODS
  Many intracellular functions have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants, including the regulation of transcription. Here, we have analyzed the impact of resveratrol on the activity of the transcription factor activator protein-1 (AP-1).
  
  
  RESULTS
  Using a chromosomally embedded AP-1-responsive reporter gene, we show that the AP-1 activity was significantly elevated in resveratrol-treated 293 human embryonic kidney and HepG2 hepatoma cells. The 12-O-tetradecanoylphorbol-13-acetate-responsive element, a binding site for c-Jun and c-Fos, was identified as resveratrol-responsive element. Expression of c-Jun and c-Fos, two proteins that constitute AP-1, is upregulated in resveratrol-stimulated HEK293 cells. On the transcriptional level, c-Jun and the ternary complex factor Elk-1 are essential for the activation of AP-1 in resveratrol-treated cells. In addition, mitogen-activated protein kinases and protein kinase C are required to connect resveratrol stimulation with enhanced AP-1 controlled transcription. Finally, we show that resveratrol increased the activities of the AP-1 responsive cyclin D1 and tumor necrosis factor α promoters.
  
  
  CONCLUSIONS
  Resveratrol regulates gene transcription via activation of stimulus-regulated protein kinases and the stimulus-responsive AP-1 transcription factors. The fact that resveratrol regulates AP-1 activity may explain many of the pleiotropic intracellular alterations induced by resveratrol.
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University of Saarland, Homburg, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Thiel
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Rössler
mesh_terms: D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C530104:CCND1 protein, human; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D013267:Stilbenes; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D019938:Cyclin D1; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D013755:Tetradecanoylphorbol Acetate; D000077185:Resveratrol
keywords: AP-1; Elk-1; MKP-1; Resveratrol; Transcription; c-Fos; c-Jun