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The ubiquitin-like protein PLIC-1 or ubiquilin 1 inhibits TLR3-Trif signaling

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).

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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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Biswas, N
Liu, S
Ronni, T
Aussenberg, SE
Liu, W
Fujita, T
Wang, T
ContributionContributors NameEmailPitt UsernameORCID
Date: 22 June 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 6
DOI or Unique Handle: 10.1371/journal.pone.0021153
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
MeSH Headings: Adaptor Proteins, Signal Transducing--metabolism; Adaptor Proteins, Vesicular Transport--metabolism; Carrier Proteins--genetics; Carrier Proteins--metabolism; Cell Cycle Proteins--genetics; Cell Cycle Proteins--metabolism; Cell Line, Tumor; Down-Regulation--drug effects; Gene Knockdown Techniques; Genes, Reporter--genetics; HEK293 Cells; Humans; Interferon-beta--genetics; Luciferases--genetics; NF-kappa B--metabolism; Newcastle disease virus--drug effects; Newcastle disease virus--physiology; Poly I-C--pharmacology; Promoter Regions, Genetic--genetics; Protein Transport--drug effects; RNA, Small Interfering--genetics; Signal Transduction--drug effects; Signal Transduction--genetics; Toll-Like Receptor 3--metabolism; Two-Hybrid System Techniques
Other ID: NLM PMC3117881
PubMed Central ID: PMC3117881
PubMed ID: 21695056
Date Deposited: 05 Sep 2012 17:36
Last Modified: 04 Feb 2019 23:55


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