Transcriptional activation of the Egr-1 gene mediated by tetradecanoylphorbol acetate and extracellular signal-regulated protein kinase

Inge Bauer; Mathias Hohl; Alia Al-Sarraj; Charles Vinson; Gerald Thiel

doi:10.1016/j.abb.2005.03.016

Transcriptional activation of the Egr-1 gene mediated by tetradecanoylphorbol acetate and extracellular signal-regulated protein kinase

Arch Biochem Biophys. 2005 Jun 1;438(1):36-52. doi: 10.1016/j.abb.2005.03.016. Epub 2005 Apr 8.

Authors

Inge Bauer¹, Mathias Hohl, Alia Al-Sarraj, Charles Vinson, Gerald Thiel

Affiliation

¹ Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, D-66421 Homburg, Germany.

PMID: 15910736
DOI: 10.1016/j.abb.2005.03.016

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism*
Cell Line, Tumor
Cyclic AMP Response Element-Binding Protein / genetics
Cyclic AMP Response Element-Binding Protein / metabolism
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism*
Dose-Response Relationship, Drug
Early Growth Response Protein 1
Extracellular Signal-Regulated MAP Kinases / genetics*
Extracellular Signal-Regulated MAP Kinases / metabolism*
Humans
Immediate-Early Proteins / genetics*
Immediate-Early Proteins / metabolism*
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism*
Recombinant Proteins / metabolism
Tetradecanoylphorbol Acetate / pharmacology*
Trans-Activators / genetics*
Trans-Activators / metabolism*
Transcription Factors / genetics*
Transcription Factors / metabolism*
Transcriptional Activation / drug effects
Transcriptional Activation / physiology*

Substances

Cyclic AMP Response Element-Binding Protein
DNA-Binding Proteins
EGR1 protein, human
Early Growth Response Protein 1
Immediate-Early Proteins
Nuclear Proteins
Recombinant Proteins
Trans-Activators
Transcription Factors
Extracellular Signal-Regulated MAP Kinases
Tetradecanoylphorbol Acetate