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Open Access Research article

EGF activates TTP expression by activation of ELK-1 and EGR-1 transcription factors

Magdalena Florkowska1, Piotr Tymoszuk1, Aleksandra Balwierz1, Anna Skucha1, Jakub Kochan1, Mateusz Wawro1, Krystyna Stalinska1 and Aneta Kasza2*

Author Affiliations

1 Deptartment of Cell Biochemistry, Jagiellonian University, Gronostajowa, Poland

2 Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland

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BMC Molecular Biology 2012, 13:8  doi:10.1186/1471-2199-13-8

Published: 20 March 2012

Abstract

Background

Tristetraprolin (TTP) is a key mediator of processes such as inflammation resolution, the inhibition of autoimmunity and in cancer. It carries out this role by the binding and degradation of mRNA transcripts, thereby decreasing their half-life. Transcripts modulated by TTP encode proteins such as cytokines, pro-inflammatory agents and immediate-early response proteins. TTP can also modulate neoplastic phenotypes in many cancers. TTP is induced and functionally regulated by a spectrum of both pro- and anti-inflammatory cytokines, mitogens and drugs in a MAPK-dependent manner. So far the contribution of p38 MAPK to the regulation of TTP expression and function has been best described.

Results

Our results demonstrate the induction of the gene coding TTP (ZFP36) by EGF through the ERK1/2-dependent pathway and implicates the transcription factor ELK-1 in this process. We show that ELK-1 regulates ZFP36 expression by two mechanisms: by binding the ZFP36 promoter directly through ETS-binding site (+ 883 to +905 bp) and by inducing expression of EGR-1, which in turn increases ZFP36 expression through sequences located between -111 and -103 bp.

Conclusions

EGF activates TTP expression via ELK-1 and EGR-1 transcription factors.