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 cytokines and the induction of c-Fos by decreasing ERK and p38 phosphorylation. GSK3β physically associates with TRAF6 in a TLR3 ligand poly I:C-dependent manner. TRAF6 is determined to be a direct E3 ligase for GSK3β, and TRAF6-mediated GSK3β ubiquitination is essential for poly I:C-dependent cytokine production by promoting the TLR3 adaptor protein TRIF-assembled signalling complex.
Mesh Terms:
Adaptor Proteins, Vesicular Transport, Animals, Cytokines, Glycogen Synthase Kinase 3, HEK293 Cells, Humans, Immunity, Innate, Inflammation, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, Mice, Mice, Knockout, Phosphorylation, Poly I-C, Proto-Oncogene Proteins c-fos, TNF Receptor-Associated Factor 6, Toll-Like Receptor 3, Ubiquitination
Nat Commun
Date: Apr. 02, 2015
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