title: EGF activates TTP expression by activation of ELK-1 and EGR-1 transcription factors.
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.
authors.affiliation: Deptartment of Cell Biochemistry, Jagiellonian University, Gronostajowa, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Florkowska
authors.forename: Piotr
authors.initials: P
authors.lastname: Tymoszuk
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Balwierz
authors.forename: Anna
authors.initials: A
authors.lastname: Skucha
authors.forename: Jakub
authors.initials: J
authors.lastname: Kochan
authors.forename: Mateusz
authors.initials: M
authors.lastname: Wawro
authors.forename: Krystyna
authors.initials: K
authors.lastname: Stalinska
authors.forename: Aneta
authors.initials: A
authors.lastname: Kasza
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015533:Transcriptional Activation; D051816:Tristetraprolin / Q000235:genetics* / Q000378:metabolism; D050807:ets-Domain Protein Elk-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D051766:Early Growth Response Protein 1; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D050807:ets-Domain Protein Elk-1; D004815:Epidermal Growth Factor