The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains

Summary: The Linear Ubiquitin Chain Assembly Complex (LUBAC), composed of HOIP, HOIL-1L, and SHARPIN, promotes tumor necrosis factor (TNF)-dependent NF-κB signaling in diverse cell types. HOIL-1L contains an Npl4 Zinc Finger (NZF) domain that specifically recognizes linear ubiquitin chains, but its...

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Autores principales:	Carlos Gomez-Diaz, Gustav Jonsson, Katrin Schodl, Luiza Deszcz, Annika Bestehorn, Kevin Eislmayr, Jorge Almagro, Anoop Kavirayani, Mayu Seida, Lilian M. Fennell, Astrid Hagelkruys, Pavel Kovarik, Josef M. Penninger, Fumiyo Ikeda
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Molecular biology Immune response Science Q
Acceso en línea:	https://doaj.org/article/50f34cedbe9040a0b591ac5680f24ec3
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spelling	oai:doaj.org-article:50f34cedbe9040a0b591ac5680f24ec32021-11-20T05:08:46ZThe ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains2589-004210.1016/j.isci.2021.103241https://doaj.org/article/50f34cedbe9040a0b591ac5680f24ec32021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012098https://doaj.org/toc/2589-0042Summary: The Linear Ubiquitin Chain Assembly Complex (LUBAC), composed of HOIP, HOIL-1L, and SHARPIN, promotes tumor necrosis factor (TNF)-dependent NF-κB signaling in diverse cell types. HOIL-1L contains an Npl4 Zinc Finger (NZF) domain that specifically recognizes linear ubiquitin chains, but its physiological role in vivo has remained unclear. Here, we demonstrate that the HOIL-1L NZF domain has important regulatory functions in inflammation and immune responses in mice. We generated knockin mice (Hoil-1lT201A;R208A/T201A;R208A) expressing a HOIL-1L NZF mutant and observed attenuated responses to TNF- and LPS-induced shock, including prolonged survival, stabilized body temperature, reduced cytokine production, and liver damage markers. Cells derived from Hoil-1lT201A;R208A/T201A;R208A mice show reduced TNF-dependent NF-κB activation and incomplete recruitment of HOIL-1L into TNF Receptor (TNFR) Complex I. We further show that HOIL-1L NZF cooperates with SHARPIN to prevent TNFR-dependent skin inflammation. Collectively, our data suggest that linear ubiquitin-chain binding by HOIL-1L regulates immune responses and inflammation in vivo.Carlos Gomez-DiazGustav JonssonKatrin SchodlLuiza DeszczAnnika BestehornKevin EislmayrJorge AlmagroAnoop KavirayaniMayu SeidaLilian M. FennellAstrid HagelkruysPavel KovarikJosef M. PenningerFumiyo IkedaElsevierarticleBiological sciencesMolecular biologyImmune responseScienceQENiScience, Vol 24, Iss 11, Pp 103241- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Molecular biology Immune response Science Q
spellingShingle	Biological sciences Molecular biology Immune response Science Q Carlos Gomez-Diaz Gustav Jonsson Katrin Schodl Luiza Deszcz Annika Bestehorn Kevin Eislmayr Jorge Almagro Anoop Kavirayani Mayu Seida Lilian M. Fennell Astrid Hagelkruys Pavel Kovarik Josef M. Penninger Fumiyo Ikeda The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains
description	Summary: The Linear Ubiquitin Chain Assembly Complex (LUBAC), composed of HOIP, HOIL-1L, and SHARPIN, promotes tumor necrosis factor (TNF)-dependent NF-κB signaling in diverse cell types. HOIL-1L contains an Npl4 Zinc Finger (NZF) domain that specifically recognizes linear ubiquitin chains, but its physiological role in vivo has remained unclear. Here, we demonstrate that the HOIL-1L NZF domain has important regulatory functions in inflammation and immune responses in mice. We generated knockin mice (Hoil-1lT201A;R208A/T201A;R208A) expressing a HOIL-1L NZF mutant and observed attenuated responses to TNF- and LPS-induced shock, including prolonged survival, stabilized body temperature, reduced cytokine production, and liver damage markers. Cells derived from Hoil-1lT201A;R208A/T201A;R208A mice show reduced TNF-dependent NF-κB activation and incomplete recruitment of HOIL-1L into TNF Receptor (TNFR) Complex I. We further show that HOIL-1L NZF cooperates with SHARPIN to prevent TNFR-dependent skin inflammation. Collectively, our data suggest that linear ubiquitin-chain binding by HOIL-1L regulates immune responses and inflammation in vivo.
format	article
author	Carlos Gomez-Diaz Gustav Jonsson Katrin Schodl Luiza Deszcz Annika Bestehorn Kevin Eislmayr Jorge Almagro Anoop Kavirayani Mayu Seida Lilian M. Fennell Astrid Hagelkruys Pavel Kovarik Josef M. Penninger Fumiyo Ikeda
author_facet	Carlos Gomez-Diaz Gustav Jonsson Katrin Schodl Luiza Deszcz Annika Bestehorn Kevin Eislmayr Jorge Almagro Anoop Kavirayani Mayu Seida Lilian M. Fennell Astrid Hagelkruys Pavel Kovarik Josef M. Penninger Fumiyo Ikeda
author_sort	Carlos Gomez-Diaz
title	The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains
title_short	The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains
title_full	The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains
title_fullStr	The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains
title_full_unstemmed	The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains
title_sort	ubiquitin ligase hoil-1l regulates immune responses by interacting with linear ubiquitin chains
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/50f34cedbe9040a0b591ac5680f24ec3
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The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains

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