Glycogen synthase kinase 3b ubiquitination by TRAF6 regulates TLR3-mediated pro-inflammatory cytokine production
نویسندگان
چکیده
TRAF6 is critical for the production of inflammatory cytokines in various TLR-mediated signalling pathways. However, it is poorly understood how TRAF6 regulates TLR3 responses. Here we demonstrate that GSK3b interacts with TRAF6 and positively regulates the TLR3-mediated signalling. Suppression of GSK3b expression or its kinase activity drastically reduces the production of inflammatory cytokines and the induction of c-Fos by decreasing ERK and p38 phosphorylation. GSK3b physically associates with TRAF6 in a TLR3 ligand poly I:C-dependent manner. TRAF6 is determined to be a direct E3 ligase for GSK3b, and TRAF6-mediated GSK3b ubiquitination is essential for poly I:C-dependent cytokine production by promoting the TLR3 adaptor protein TRIF-assembled signalling complex. DOI: 10.1038/ncomms7765 OPEN
منابع مشابه
Glycogen synthase kinase 3β ubiquitination by TRAF6 regulates TLR3-mediated pro-inflammatory cytokine production
TRAF6 is critical for the production of inflammatory cytokines in various TLR-mediated signalling pathways. However, it is poorly understood how TRAF6 regulates TLR3 responses. Here we demonstrate that GSK3β interacts with TRAF6 and positively regulates the TLR3-mediated signalling. Suppression of GSK3β expression or its kinase activity drastically reduces the production of inflammatory cytokin...
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