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Sci. Signal., 1 October 2013
Vol. 6, Issue 295, p. ra86
[DOI: 10.1126/scisignal.2004301]

RESEARCH ARTICLES

Depletion of the 26S Proteasome Adaptor Ecm29 Increases Toll-Like Receptor 3 Signaling

Carlos Gorbea1*{dagger}, Martin Rechsteiner2, Jesús G. Vallejo3, and Neil E. Bowles1{dagger}

1 Division of Cardiology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
2 Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
3 Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine and Texas Children’s Hospital, 1102 Bates Street, FC 430.09, Houston, TX 77030, USA.

* Present address: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

Abstract: Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA and stimulates the innate immune response. We found that depletion of extracellular mutant 29 (Ecm29), an adaptor protein that binds to a subset of 26S proteasomes (Ecm proteasomes), increased the abundance of TLR3 in human embryonic kidney–293 and HeLa cells. Loss of Ecm29 also increased the amounts of LC3β and p62, two proteins that mediate autophagy. The absence of Ecm29 enhanced TLR3 signaling, which was characterized by the increased abundance of the adaptor protein and E3 ubiquitin ligase tumor necrosis factor receptor–associated factor 3, increased phosphorylation and activation of effector kinases downstream of TLR3, increased nuclear localization of the transcription factor interferon regulatory factor 3, and the accumulation of signaling molecules at juxtanuclear recycling endosomes. We conclude that Ecm proteasomes play a previously uncharacterized role in mediating autophagy, trafficking of TLR3, and attenuation of TLR3-dependent signaling.

{dagger} Corresponding author. E-mail: neil.bowles{at}hsc.utah.edu (N.E.B.); gorbea{at}biochem.utah.edu (C.G.)

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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