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Mitochondrial Ubiquitin Ligase MARCH5 Promotes TLR7 Signaling by Attenuating TANK Action

The signaling of Toll-like receptors (TLRs) is the host's first line of defense against microbial invasion. The mitochondrion is emerging as a critical platform for antiviral signal transduction. The regulatory role of mitochondria for TLR signaling remains to be explored. Here, we show that th...

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Detalles Bibliográficos
Autores principales: Shi, He-Xin, Liu, Xing, Wang, Qiang, Tang, Pei-Pei, Liu, Xin-Yi, Shan, Yu-Fei, Wang, Chen
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098239/
https://www.ncbi.nlm.nih.gov/pubmed/21625535
http://dx.doi.org/10.1371/journal.ppat.1002057
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author Shi, He-Xin
Liu, Xing
Wang, Qiang
Tang, Pei-Pei
Liu, Xin-Yi
Shan, Yu-Fei
Wang, Chen
author_facet Shi, He-Xin
Liu, Xing
Wang, Qiang
Tang, Pei-Pei
Liu, Xin-Yi
Shan, Yu-Fei
Wang, Chen
author_sort Shi, He-Xin
collection PubMed
description The signaling of Toll-like receptors (TLRs) is the host's first line of defense against microbial invasion. The mitochondrion is emerging as a critical platform for antiviral signal transduction. The regulatory role of mitochondria for TLR signaling remains to be explored. Here, we show that the mitochondrial outer-membrane protein MARCH5 positively regulates TLR7 signaling. Ectopic expression or knockdown of MARCH5 enhances or impairs NF-κB-mediated gene expression, respectively. MARCH5 interacts specifically with TANK, and this interaction is enhanced by R837 stimulation. MARCH5 catalyzes the K63-linked poly-ubiquitination of TANK on its Lysines 229, 233, 280, 302 and 306, thus impairing the ability of TANK to inhibit TRAF6. Mislocalization of MARCH5 abolishes its action on TANK, revealing the critical role of mitochondria in modulating innate immunity. Arguably, this represents the first study linking mitochondria to TLR signaling.
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spelling pubmed-30982392011-05-27 Mitochondrial Ubiquitin Ligase MARCH5 Promotes TLR7 Signaling by Attenuating TANK Action Shi, He-Xin Liu, Xing Wang, Qiang Tang, Pei-Pei Liu, Xin-Yi Shan, Yu-Fei Wang, Chen PLoS Pathog Research Article The signaling of Toll-like receptors (TLRs) is the host's first line of defense against microbial invasion. The mitochondrion is emerging as a critical platform for antiviral signal transduction. The regulatory role of mitochondria for TLR signaling remains to be explored. Here, we show that the mitochondrial outer-membrane protein MARCH5 positively regulates TLR7 signaling. Ectopic expression or knockdown of MARCH5 enhances or impairs NF-κB-mediated gene expression, respectively. MARCH5 interacts specifically with TANK, and this interaction is enhanced by R837 stimulation. MARCH5 catalyzes the K63-linked poly-ubiquitination of TANK on its Lysines 229, 233, 280, 302 and 306, thus impairing the ability of TANK to inhibit TRAF6. Mislocalization of MARCH5 abolishes its action on TANK, revealing the critical role of mitochondria in modulating innate immunity. Arguably, this represents the first study linking mitochondria to TLR signaling. Public Library of Science 2011-05-19 /pmc/articles/PMC3098239/ /pubmed/21625535 http://dx.doi.org/10.1371/journal.ppat.1002057 Text en Shi et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Shi, He-Xin
Liu, Xing
Wang, Qiang
Tang, Pei-Pei
Liu, Xin-Yi
Shan, Yu-Fei
Wang, Chen
Mitochondrial Ubiquitin Ligase MARCH5 Promotes TLR7 Signaling by Attenuating TANK Action
title Mitochondrial Ubiquitin Ligase MARCH5 Promotes TLR7 Signaling by Attenuating TANK Action
title_full Mitochondrial Ubiquitin Ligase MARCH5 Promotes TLR7 Signaling by Attenuating TANK Action
title_fullStr Mitochondrial Ubiquitin Ligase MARCH5 Promotes TLR7 Signaling by Attenuating TANK Action
title_full_unstemmed Mitochondrial Ubiquitin Ligase MARCH5 Promotes TLR7 Signaling by Attenuating TANK Action
title_short Mitochondrial Ubiquitin Ligase MARCH5 Promotes TLR7 Signaling by Attenuating TANK Action
title_sort mitochondrial ubiquitin ligase march5 promotes tlr7 signaling by attenuating tank action
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098239/
https://www.ncbi.nlm.nih.gov/pubmed/21625535
http://dx.doi.org/10.1371/journal.ppat.1002057
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