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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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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. |
format | Online Article Text |
id | pubmed-3457734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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