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Stress induced gene expression

Stress induced gene expression : a direct role for MAPKAP kinases in transcriptional activation of immediate early genes

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Authors

  • N. Ronkina
  • M. B. Menon
  • J. Schwermann
  • J. S. C. Arthur
  • H. Legault
  • J. -B. Telliez
  • U. S. Kayyali
  • A. R. Nebreda
  • A. Kotlyarov
  • M. Gaestel

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Info

Original languageEnglish
Pages2503-2518
Number of pages16
JournalNucleic Acids Research
Journal publication dateApr 2011
Journal number7
Volume39
DOIs
StatePublished

Abstract

Immediate early gene (IEG) expression is coordinated by multiple MAP kinase signaling pathways in a signal specific manner. Stress-activated p38 alpha MAP kinase is implicated in transcriptional regulation of IEGs via MSK-mediated CREB phosphorylation. The protein kinases downstream to p38, MAPKAP kinase (MK) 2 and MK3 have been identified to regulate gene expression at the posttranscriptional levels of mRNA stability and translation. Here, we analyzed stress-induced IEG expression in MK2/3-deficient cells. Ablation of MKs causes a decrease of p38 alpha level and p38-dependent IEG expression. Unexpectedly, restoration of p38 alpha does not rescue the full-range IEG response. Instead, the catalytic activity of MKs is necessary for the major transcriptional activation of IEGs. By transcriptomics, we identified MK2-regulated genes and recognized the serum response element (SRE) as a common promoter element. We show that stress-induced phosphorylation of serum response factor (SRF) at serine residue 103 is significantly reduced and that induction of SRE-dependent reporter activity is impaired and can only be rescued by catalytically active MK2 in MK2/3-deficient cells. Hence, a new function of MKs in transcriptional activation of IEGs via the p38 alpha-MK2/3-SRF-axis is proposed which probably cooperates with MKs' role in posttranscriptional gene expression in inflammation and stress response.

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