Transcriptional activation of the Egr-1 gene mediated by tetradecanoylphorbol acetate and extracellular signal-regulated protein kinase.
Activation of extracellular signal-regulated protein kinase (ERK) triggers the biosynthesis of Egr-1, a zinc finger transcription factor. Likewise, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) strongly upregulates Egr-1 biosynthesis. Here, we have analyzed the genetic elements involved in the regulation of Egr-1 gene transcription by ERK and TPA in human hepatoma cells. Expression experiments using mitogen-activated protein kinase phosphatase-1 or a dominant-negative mutant of the ternary complex factor Elk-1 revealed that the distal cluster of serum response elements is essential in the TPA-induced enhancement of Egr-1 promoter activity, encompassing two independent TPA-responsive elements. The CRE in the proximal Egr-1 promoter plays, if anything, only a marginal role in TPA-induced stimulus-transcription coupling of the Egr-1 gene. The fact that Egr-1 promoter/reporter gene transcription is upregulated by a constitutively active CREB mutant indicates that the CRE couples other signaling cascades via CREB to the Egr-1 gene.
Bauer
Inge
I
Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, D-66421 Homburg, Germany.
Hohl
Mathias
M
Al-Sarraj
Alia
A
Vinson
Charles
C
Thiel
Gerald
G
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate