Sci. Signal., 1 October 2013
Ecm Proteasomes Inhibit Antiviral ResponsesToll-like receptor 3 (TLR3) is an endosomal pattern recognition receptor that recognizes viral double-stranded RNA and stimulates the production of type I interferon (IFN) as part of the antiviral immune response. Mutations in TLR3 that lead to decreased TLR3 signaling result in the development of immunodeficiencies in humans. Gorbea et al. found that depletion of Ecm29, an adaptor protein associated with a subset of 26S proteasomes, inhibited autophagy and enhanced TLR3 signaling. In Ecm29-deficient cells, TLR3 and its effectors accumulated at perinuclear sites. Inhibition of proteasomal activity or displacement of Ecm29 from autophagic vesicles potentiated type I IFN production in response to TLR3 stimulation. Together, these data suggest that Ecm29 mediates the autophagic attenuation of TLR3 signaling and suggest cooperation between proteasomal degradation and autophagic degradation in controlling the antiviral response.
Citation: C. Gorbea, M. Rechsteiner, J. G. Vallejo, N. E. Bowles, Depletion of the 26S Proteasome Adaptor Ecm29 Increases Toll-Like Receptor 3 Signaling. Sci. Signal. 6, ra86 (2013).
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