Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA

Stable Identifier
R-HSA-450513
Type
Pathway
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser

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.
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.

Literature References
PubMed ID Title Journal Year
16391004 AU-rich elements and associated factors: are there unifying principles?

Barreau, C, Paillard, L, Osborne, HB

Nucleic Acids Res 2005
18481987 Control of mRNA decay by phosphorylation of tristetraprolin

Sandler, H, Stoecklin, G

Biochem Soc Trans 2008
12704645 Post-transcriptional regulation of gene expression by degradation of messenger RNAs

Bevilacqua, A, Ceriani, MC, Capaccioli, S, Nicolin, A

J Cell Physiol 2003
12440953 AU-rich element-mediated translational control: complexity and multiple activities of trans-activating factors

Zhang, T, Kruys, V, Huez, G, Gueydan, C

Biochem Soc Trans 2002
Participants
Participant Of
Event Information
Orthologous Events
Authored
Reviewed
Created