HuR is required for IL-17-induced Act1-mediated CXCL1 and CXCL5 mRNA stabilization.
IL-17, a major inflammatory cytokine plays a critical role in the pathogenesis of many autoimmune inflammatory diseases. In this study, we report a new function of RNA-binding protein HuR in IL-17-induced Act1-mediated chemokine mRNA stabilization. HuR deficiency markedly reduced IL-17-induced chemokine expression due to increased mRNA decay. Act1-mediated HuR polyubiquitination ... was required for the binding of HuR to CXCL1 mRNA, leading to mRNA stabilization. Although IL-17 induced the coshift of Act1 and HuR to the polysomal fractions in a sucrose gradient, HuR deficiency reduced the ratio of translation-active/translation-inactive IL-17-induced chemokine mRNAs. Furthermore, HuR deletion in distal lung epithelium attenuated IL-17-induced neutrophilia. In summary, HuR functions to couple receptor-proximal signaling to posttranscriptional machinery, contributing to IL-17-induced inflammation.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Cell Line, Chemokine CXCL1, Chemokine CXCL5, HeLa Cells, Hu Paraneoplastic Encephalomyelitis Antigens, Humans, Inflammation, Interleukin-17, Lung, Mice, Mice, Knockout, Protein Binding, RNA Stability, RNA, Messenger, Respiratory Mucosa, Signal Transduction, Ubiquitination
Adaptor Proteins, Signal Transducing, Animals, Cell Line, Chemokine CXCL1, Chemokine CXCL5, HeLa Cells, Hu Paraneoplastic Encephalomyelitis Antigens, Humans, Inflammation, Interleukin-17, Lung, Mice, Mice, Knockout, Protein Binding, RNA Stability, RNA, Messenger, Respiratory Mucosa, Signal Transduction, Ubiquitination
J. Immunol.
Date: Jul. 15, 2013
PubMed ID: 23772036
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