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Figure 4. Molecular actions of TTP to ensure that rapid mRNA decay is mediated through p38 MAPK signaling. In the absence of inflammatory stimulation, TTP binds ARE cytokine mRNA and shuttles the message to exosomal and P-body degradation sites, where mRNA is degraded by exonucleases in the 3' to 5' direction or the 5' to 3' direction, respectively. Upon activation of the p38 MAPK-MK2 pathway, TTP is phosphorylated at serines 52 and 178. Phosphorylation at these sites sequesters TTP from ARE mRNA and allows for interaction with 14-3-3 proteins. The ARE mRNAs are now capable of interacting with stabilizing components, which shuttle the transcript to translational machinery (see text for details).
