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TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1

TANK-binding kinase 1 (TBK1) plays an essential role in Toll-like receptor (TLR)– and retinoic acid–inducible gene I (RIG-I)–mediated induction of type I interferon (IFN; IFN-α/β) and host antiviral responses. How TBK1 activity is negatively regulated remains largely unknown. We report that TNF rece...

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Autores principales: Zhang, Meng, Wang, Lijuan, Zhao, Xueying, Zhao, Kai, Meng, Hong, Zhao, Wei, Gao, Chengjiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457734/
https://www.ncbi.nlm.nih.gov/pubmed/22945920
http://dx.doi.org/10.1084/jem.20120024
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author Zhang, Meng
Wang, Lijuan
Zhao, Xueying
Zhao, Kai
Meng, Hong
Zhao, Wei
Gao, Chengjiang
author_facet Zhang, Meng
Wang, Lijuan
Zhao, Xueying
Zhao, Kai
Meng, Hong
Zhao, Wei
Gao, Chengjiang
author_sort Zhang, Meng
collection PubMed
description TANK-binding kinase 1 (TBK1) plays an essential role in Toll-like receptor (TLR)– and retinoic acid–inducible gene I (RIG-I)–mediated induction of type I interferon (IFN; IFN-α/β) and host antiviral responses. How TBK1 activity is negatively regulated remains largely unknown. We report that TNF receptor-associated factor (TRAF)–interacting protein (TRIP) promotes proteasomal degradation of TBK1 and inhibits TLR3/4- and RIG-I–induced IFN-β signaling. TRIP knockdown resulted in augmented activation of IFN regulatory factor 3 (IRF3) and enhanced expression of IFN-β in TLR3/4- and RIG-I–activated primary peritoneal macrophages, whereas overexpression of TRIP had opposite effects. Consistently, TRIP impaired Sendai virus (SeV) infection–induced IRF3 activation and IFN-β production and promoted vesicular stomatitis virus (VSV) replication. As an E3 ubiquitin ligase, TRIP negatively regulated the cellular levels of TBK1 by directly binding to and promoting K48-linked polyubiquitination of TBK1. Therefore, we identified TRIP as a negative regulator in TLR3/4- and RIG-I–triggered antiviral responses and suggested TRIP as a potential target for the intervention of diseases with uncontrolled IFN-β production.
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spelling pubmed-34577342013-03-24 TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1 Zhang, Meng Wang, Lijuan Zhao, Xueying Zhao, Kai Meng, Hong Zhao, Wei Gao, Chengjiang J Exp Med Brief Definitive Report TANK-binding kinase 1 (TBK1) plays an essential role in Toll-like receptor (TLR)– and retinoic acid–inducible gene I (RIG-I)–mediated induction of type I interferon (IFN; IFN-α/β) and host antiviral responses. How TBK1 activity is negatively regulated remains largely unknown. We report that TNF receptor-associated factor (TRAF)–interacting protein (TRIP) promotes proteasomal degradation of TBK1 and inhibits TLR3/4- and RIG-I–induced IFN-β signaling. TRIP knockdown resulted in augmented activation of IFN regulatory factor 3 (IRF3) and enhanced expression of IFN-β in TLR3/4- and RIG-I–activated primary peritoneal macrophages, whereas overexpression of TRIP had opposite effects. Consistently, TRIP impaired Sendai virus (SeV) infection–induced IRF3 activation and IFN-β production and promoted vesicular stomatitis virus (VSV) replication. As an E3 ubiquitin ligase, TRIP negatively regulated the cellular levels of TBK1 by directly binding to and promoting K48-linked polyubiquitination of TBK1. Therefore, we identified TRIP as a negative regulator in TLR3/4- and RIG-I–triggered antiviral responses and suggested TRIP as a potential target for the intervention of diseases with uncontrolled IFN-β production. The Rockefeller University Press 2012-09-24 /pmc/articles/PMC3457734/ /pubmed/22945920 http://dx.doi.org/10.1084/jem.20120024 Text en © 2012 Zhang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Zhang, Meng
Wang, Lijuan
Zhao, Xueying
Zhao, Kai
Meng, Hong
Zhao, Wei
Gao, Chengjiang
TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1
title TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1
title_full TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1
title_fullStr TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1
title_full_unstemmed TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1
title_short TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1
title_sort traf-interacting protein (trip) negatively regulates ifn-β production and antiviral response by promoting proteasomal degradation of tank-binding kinase 1
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457734/
https://www.ncbi.nlm.nih.gov/pubmed/22945920
http://dx.doi.org/10.1084/jem.20120024
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