title: Resveratrol upregulates Egr-1 expression and activity involving extracellular signal-regulated protein kinase and ternary complex factors.
abstract: Many intracellular functions have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants. Here, we show that resveratrol induces the expression of the transcription factor Egr-1 in human embryonic kidney cells. Using a chromosomally embedded Egr-1-responsive reporter gene, we show that the Egr-1 activity was significantly elevated in resveratrol-treated cells, indicating that the newly synthesized Egr-1 protein was biologically active. Stimulus-transcription coupling leading to the resveratrol-induced upregulation of Egr-1 expression and activity requires the protein kinases Raf and extracellular signal-regulated protein kinase ERK, while MAP kinase phosphatase-1 functions as a nuclear shut-off device that interrupts the signaling cascade connecting resveratrol stimulation with enhanced Egr-1 expression. On the transcriptional level, Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, connects the intracellular signaling cascade elicited by resveratrol with transcription of the Egr-1 gene. These data were corroborated by the observation that stimulation of the cells with resveratrol increased the transcriptional activation potential of Elk-1. The SRE as well as the GC-rich DNA binding site of Egr-1 function as resveratrol-responsive elements. Thus, resveratrol regulates gene transcription via activation of the stimulus-regulated protein kinases Raf and ERK and the stimulus-responsive transcription factors TCF and Egr-1.
authors: Department of Medical Biochemistry and Molecular Biology, University of Saarland, D-66421 Homburg, Germany.
authors: Oliver G
authors: OG
authors: Rössler
authors: Department of Medical Biochemistry and Molecular Biology, University of Saarland, D-66421 Homburg, Germany.
authors: Daniel
authors: D
authors: Glatzel
authors: Department of Medical Biochemistry and Molecular Biology, University of Saarland, D-66421 Homburg, Germany. Electronic address: gerald.thiel@uks.eu.
authors: Gerald
authors: G
authors: Thiel
mesh_terms: D001483:Base Sequence; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D020218:Response Elements; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation; D050807:ets-Domain Protein Elk-1 / Q000502:physiology*
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D013267:Stilbenes; D050807:ets-Domain Protein Elk-1; D048049:Extracellular Signal-Regulated MAP Kinases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D000077185:Resveratrol
keywords: ERK; Egr-1; Elk-1; Lentivirus; Resveratrol; Transcription