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

Int J Biochem Cell Biol. 2018 Jan:94:6-9. doi: 10.1016/j.biocel.2017.11.003. Epub 2017 Nov 8.

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.

Keywords: Adenosine/uridine-rich element; Inflammation; MAPK p38; Post-transcriptional regulation; Tristetraprolin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Enzyme Activation
  • Gene Expression Regulation*
  • Humans
  • Immune System / enzymology
  • Immune System / metabolism*
  • Inflammation / enzymology
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • MAP Kinase Signaling System*
  • Models, Immunological*
  • Phosphorylation
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / metabolism
  • Proteolysis
  • Tristetraprolin / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Tristetraprolin
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Proteasome Endopeptidase Complex