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This Podcast features an interview with Carlos Gorbea, author of a Research Article that appears in the 1 October 2013 issue of Science Signaling on the role of proteasomes in TLR3 signaling. TLR3 is a member of the Toll-like receptor family, which is a group of related receptors that detect the presence of pathogens and trigger innate immune responses. TLR3 is localized to endosomes and activated by binding to double-stranded RNA, which is the genetic material of some viruses. Gorbea and colleagues found that depletion of Ecm29, which is an adaptor protein associated with a subset of 26S proteasomes, increased TLR3 signaling by inhibiting both the proteasomal degradation of TLR3 effectors and the autophagic degradation of TLR3 and TLR3 effectors.