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RNF144B inhibits LPS‐induced inflammatory responses via binding TBK1

Innate immune responses need to be precisely controlled to avoid prolonged inflammation and prevent unwanted damage to the host. Here, we report that RNF144B responded dynamically to LPS stimulation and negatively regulated LPS‐induced inflammation. We found that RNF144B interacted with the scaffold...

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Autores principales: Zhang, Zhen, Zhang, Luoyan, Wang, Bin, Zhu, Xiaoxiao, Zhao, Lin, Chu, Chu, Guo, Qiang, Wei, Ran, Yin, Xunqiang, Zhang, Yunhong, Li, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899866/
https://www.ncbi.nlm.nih.gov/pubmed/31509299
http://dx.doi.org/10.1002/JLB.2A0819-055R
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author Zhang, Zhen
Zhang, Luoyan
Wang, Bin
Zhu, Xiaoxiao
Zhao, Lin
Chu, Chu
Guo, Qiang
Wei, Ran
Yin, Xunqiang
Zhang, Yunhong
Li, Xia
author_facet Zhang, Zhen
Zhang, Luoyan
Wang, Bin
Zhu, Xiaoxiao
Zhao, Lin
Chu, Chu
Guo, Qiang
Wei, Ran
Yin, Xunqiang
Zhang, Yunhong
Li, Xia
author_sort Zhang, Zhen
collection PubMed
description Innate immune responses need to be precisely controlled to avoid prolonged inflammation and prevent unwanted damage to the host. Here, we report that RNF144B responded dynamically to LPS stimulation and negatively regulated LPS‐induced inflammation. We found that RNF144B interacted with the scaffold/dimerization domain (SDD) of TANK binding kinase 1 (TBK1) through the in between RING (IBR) domain to inhibit its phosphorylation and K63‐linked polyubiquitination, which led to TBK1 inactivation, IRF3 dephosphorylation, and IFN‐β reduction. RNF144B knockdown with siRNA increased IRF3 activation and IFN‐β production in response to LPS stimulation. Our study identifies that RNF144B interaction with TBK1 is sufficient to inactivate TBK1 and delineates a previously unrecognized role for RNF144B in innate immune responses.
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spelling pubmed-68998662019-12-19 RNF144B inhibits LPS‐induced inflammatory responses via binding TBK1 Zhang, Zhen Zhang, Luoyan Wang, Bin Zhu, Xiaoxiao Zhao, Lin Chu, Chu Guo, Qiang Wei, Ran Yin, Xunqiang Zhang, Yunhong Li, Xia J Leukoc Biol Receptors, Signal Transduction, & Genes Innate immune responses need to be precisely controlled to avoid prolonged inflammation and prevent unwanted damage to the host. Here, we report that RNF144B responded dynamically to LPS stimulation and negatively regulated LPS‐induced inflammation. We found that RNF144B interacted with the scaffold/dimerization domain (SDD) of TANK binding kinase 1 (TBK1) through the in between RING (IBR) domain to inhibit its phosphorylation and K63‐linked polyubiquitination, which led to TBK1 inactivation, IRF3 dephosphorylation, and IFN‐β reduction. RNF144B knockdown with siRNA increased IRF3 activation and IFN‐β production in response to LPS stimulation. Our study identifies that RNF144B interaction with TBK1 is sufficient to inactivate TBK1 and delineates a previously unrecognized role for RNF144B in innate immune responses. John Wiley and Sons Inc. 2019-09-11 2019-12 /pmc/articles/PMC6899866/ /pubmed/31509299 http://dx.doi.org/10.1002/JLB.2A0819-055R Text en © 2019 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Receptors, Signal Transduction, & Genes
Zhang, Zhen
Zhang, Luoyan
Wang, Bin
Zhu, Xiaoxiao
Zhao, Lin
Chu, Chu
Guo, Qiang
Wei, Ran
Yin, Xunqiang
Zhang, Yunhong
Li, Xia
RNF144B inhibits LPS‐induced inflammatory responses via binding TBK1
title RNF144B inhibits LPS‐induced inflammatory responses via binding TBK1
title_full RNF144B inhibits LPS‐induced inflammatory responses via binding TBK1
title_fullStr RNF144B inhibits LPS‐induced inflammatory responses via binding TBK1
title_full_unstemmed RNF144B inhibits LPS‐induced inflammatory responses via binding TBK1
title_short RNF144B inhibits LPS‐induced inflammatory responses via binding TBK1
title_sort rnf144b inhibits lps‐induced inflammatory responses via binding tbk1
topic Receptors, Signal Transduction, & Genes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899866/
https://www.ncbi.nlm.nih.gov/pubmed/31509299
http://dx.doi.org/10.1002/JLB.2A0819-055R
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