MAPK p38 regulates inflammatory gene expression via tristetraprolin: Doing good by stealth

Research output: Contribution to journalArticlepeer-review

Authors

External organisations

  • Woolcock Emphysema Centre, Woolcock Institute of Medical Research, University of Sydney

Abstract

Tristetraprolin (TTP) is an RNA-destabilizing protein that exerts profound anti-inflammatory effects by inhibiting the expression of tumour necrosis factor and many other inflammatory mediators. The mitogen-activated protein kinase (MAPK) p38 signaling pathway controls the strength and duration of inflammatory responses by regulating both the expression and function of TTP. The kinase MK2 (MAPK activated kinase 2) is activated by MAPK p38, and in turn phosphorylates TTP at two critical serine residues. One consequence of these phosphorylations is the protection of TTP from proteasome-mediated degradation. Another consequence is the loss of mRNA destabilizing activity. The control of TTP expression and function by the MAPK p38 pathway provides an elegant mechanism for coupling the on and off phases of inflammatory responses, and dictating the precise kinetics of expression of individual inflammatory mediators.

Details

Original languageEnglish
Pages (from-to)6-9
Number of pages4
JournalThe International Journal of Biochemistry & Cell Biology
Volume94
Early online date8 Nov 2017
Publication statusPublished - Jan 2018

Keywords

  • MAPK p38, Tristetraprolin , post-transcriptional regulation , inflammation , Adenosine/uridine-rich element