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Figure 3. RNA-binding proteins mediate regulation of cytokine mRNA stability through p38/MK2 signaling. LPS activates p38 MAPK signaling in a variety of cells, leading to transcriptional activation of cytokine genes or enhanced mRNA stability and translation (highlighted areas). The fate of ARE mRNA is dependent on the presence of destabilizing and stabilizing mRNA binding proteins. p38 MAPK activates MK2 in the nucleus, allowing for MK2 translocation to the cytoplasm. MK2 subsequently phosphorylates destabilizing mRNA-binding proteins such as TTP. This action prevents TTP from interacting with ARE cytokines. Simultaneously, activation of the p38 MAPK pathway results in translocation of HuR, a stabilizing RNA-binding protein, from the nucleus to the cytoplasm. Thus, upon p38/MK2 activation and phosphorylation of TTP, cytokine mRNA stability is enhanced, because TTP is no longer dictating mRNA triage and exonuclease decay.
