PathwayStep361 PathwayStep362 PathwayStep363 PathwayStep364 Phosphorylated Tristetraproline (TTP) binds 14-3-3beta TTP Recruits RNA Degradation Activities Phosphorylation of Tristetraproline (TTP) by MK2 Tristetraproline (TTP) Binds AU-rich Elements in 3' UTR of Target mRNAs Destabilization of mRNA by Tristetraprolin (TTP) Authored: May, B, 2009-12-29 Edited: May, B, 2009-12-29 Pubmed12440953 Pubmed12704645 Pubmed16391004 Pubmed18481987 Reactome Database ID Release 43450513 Reactome, http://www.reactome.org ReactomeREACT_25064 Reviewed: Wilusz, J, 2010-06-29 Tristetraproline (TTP) binds RNAs that contain AU-rich elements and recruits enzymes that degrade RNA. TTP interacts with the exosome (3' to 5' exonuclease), XRN1 (5' to 3' exonuclease), and the decapping enzymes DCP1 and DCP2a.<br>The activity of TTP is regulated by phosphorylation. MK2 phosphorylates TTP, which then binds 14-3-3.The interaction with 14-3-3 prevents phosphorylated TTP from entering stress granules and stabilizes mRNA bound by phosphorylated TTP. Tristetraproline is known to bind AU-rich elements in the following mRNAs: Tumor necrosis factor alpha (TNFA), Granulocyte-macrophage colony stimulating factor (CSF2, GM-CSF), Interleukin-2 (IL-2), and Proto-oncogene C-FOS (FOS, c-fos). Mice deficient in TTP exhibit arthritis, weight loss, skin lesions, autoimmunity, and myeloid hyperplasia.