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BMC Mol Biol. 2012; 13: 8.
Published online Mar 20, 2012. doi:  10.1186/1471-2199-13-8
PMCID: PMC3342124
EGF activates TTP expression by activation of ELK-1 and EGR-1 transcription factors
Magdalena Florkowska,#1 Piotr Tymoszuk,#1 Aleksandra Balwierz,1 Anna Skucha,1 Jakub Kochan,1 Mateusz Wawro,1 Krystyna Stalinska,1 and Aneta Kaszacorresponding author2
1Deptartment of Cell Biochemistry, Jagiellonian University, Gronostajowa, Poland
2Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland
corresponding authorCorresponding author.
#Contributed equally.
Magdalena Florkowska: m.florkowska/at/gmail.com; Piotr Tymoszuk: Piotr.Tymoszuk/at/i-med.ac.at; Aleksandra Balwierz: ardnaskela_z/at/o2.pl; Anna Skucha: a2nia/at/tlen.pl; Jakub Kochan: kochan.jakub/at/gmail.com; Mateusz Wawro: mateusz.wawro/at/uj.edu.pl; Krystyna Stalinska: krysiasta/at/interia.pl; Aneta Kasza: aneta.kasza/at/uj.edu.pl
Received October 28, 2011; Accepted March 20, 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.
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