relation: http://d-scholarship-dev.library.pitt.edu/13871/
title: The ubiquitin-like protein PLIC-1 or ubiquilin 1 inhibits TLR3-Trif signaling
creator: Biswas, N
creator: Liu, S
creator: Ronni, T
creator: Aussenberg, SE
creator: Liu, W
creator: Fujita, T
creator: Wang, T
description: Background: The innate immune responses to virus infection are initiated by either Toll-like receptors (TLR3/7/8/9) or cytoplasmic double-stranded RNA (dsRNA)-recognizing RNA helicases RIG-I and MDA5. To avoid causing injury to the host, these signaling pathways must be switched off in time by negative regulators. Methodology/Principal Findings: Through yeast-two hybrid screening, we found that an ubiquitin-like protein named protein linking integrin-associated protein to cytoskeleton 1(PLIC-1 or Ubiquilin 1) interacted with the Toll/interleukin-1 receptor (TIR) domain of TLR4. Interestingly, PLIC-1 had modest effect on TLR4-mediated signaling, but strongly suppressed the transcriptional activation of IFN-β promoter through the TLR3-Trif-dependent pathway. Concomitantly, reduction of endogenous PLIC-1 by short-hairpin interfering RNA (shRNA) enhanced TLR3 activation both in luciferase reporter assays as well as in new castle disease virus (NDV) infected cells. An interaction between PLIC-1 and Trif was confirmed in co-immunoprecipitation (Co-IP) and GST-pull-down assays. Subsequent confocal microscopic analysis revealed that PLIC-1 and Trif colocalized with the autophagosome marker LC3 in punctate subcellular structures. Finally, overexpression of PLIC-1 decreased Trif protein abundance in a Nocodazole-sensitive manner. Conclusions: Our results suggest that PLIC-1 is a novel inhibitor of the TLR3-Trif antiviral pathway by reducing the abundance of Trif. © 2011 Biswas et al.
date: 2011-06-22
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/13871/1/The_Ubiquitin-Like_Protein.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/13871/8/licence.txt
identifier:   Biswas, N and Liu, S and Ronni, T and Aussenberg, SE and Liu, W and Fujita, T and Wang, T  (2011) The ubiquitin-like protein PLIC-1 or ubiquilin 1 inhibits TLR3-Trif signaling.  PLoS ONE, 6 (6).       
relation: 10.1371/journal.pone.0021153