Control of mRNA decay by phosphorylation of tristetraprolin

Biochem Soc Trans. 2008 Jun;36(Pt 3):491-6. doi: 10.1042/BST0360491.

Abstract

TTP (tristetraprolin) is an RNA-binding protein that suppresses inflammation by accelerating the degradation of cytokine mRNAs. TTP binds to an AU-rich element in the 3'-untranslated region of its target mRNAs. In macrophages, the induction of cytokine expression requires activation of the p38-MAPK (mitogen-activated protein kinase)-MK2 [MAPKAP (MAPK-activated protein) kinase-2] kinase cascade. MK2 directly phosphorylates TTP and thereby contributes to transient stabilization of cytokine mRNAs. In the present review, we address the target specificity of TTP, summarize TTP-interacting proteins and discuss how phosphorylation regulates the activity, localization and stability of TTP.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Cytoplasmic Structures / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • RNA Stability*
  • Tristetraprolin / metabolism*

Substances

  • Cytokines
  • Intracellular Signaling Peptides and Proteins
  • Tristetraprolin
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases