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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Autores principales:	He-Xin Shi, Xing Liu, Qiang Wang, Pei-Pei Tang, Xin-Yi Liu, Yu-Fei Shan, Chen Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8e788d95bf234c538535a9a20d08e7ed
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spelling	oai:doaj.org-article:8e788d95bf234c538535a9a20d08e7ed2021-11-18T06:03:23ZMitochondrial ubiquitin ligase MARCH5 promotes TLR7 signaling by attenuating TANK action.1553-73661553-737410.1371/journal.ppat.1002057https://doaj.org/article/8e788d95bf234c538535a9a20d08e7ed2011-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21625535/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The 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.He-Xin ShiXing LiuQiang WangPei-Pei TangXin-Yi LiuYu-Fei ShanChen WangPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 5, p e1002057 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 He-Xin Shi Xing Liu Qiang Wang Pei-Pei Tang Xin-Yi Liu Yu-Fei Shan Chen Wang Mitochondrial ubiquitin ligase MARCH5 promotes TLR7 signaling by attenuating TANK action.
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.
format	article
author	He-Xin Shi Xing Liu Qiang Wang Pei-Pei Tang Xin-Yi Liu Yu-Fei Shan Chen Wang
author_facet	He-Xin Shi Xing Liu Qiang Wang Pei-Pei Tang Xin-Yi Liu Yu-Fei Shan Chen Wang
author_sort	He-Xin Shi
title	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_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_sort	mitochondrial ubiquitin ligase march5 promotes tlr7 signaling by attenuating tank action.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/8e788d95bf234c538535a9a20d08e7ed
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Mitochondrial ubiquitin ligase MARCH5 promotes TLR7 signaling by attenuating TANK action.

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