Control of mRNA decay by phosphorylation of tristetraprolin.
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.
Sandler
Heike
H
Helmholtz Junior Research Group Post-transcriptional Control of Gene Expression, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Stoecklin
Georg
G
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D022083:Cytoplasmic Structures / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020871:RNA Stability; D051816:Tristetraprolin / Q000378:metabolism*; D000099190:MAP-Kinase-Activated Kinase 2
D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D051816:Tristetraprolin; D000099190:MAP-Kinase-Activated Kinase 2