E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis

Gasdermin D (GSDMD) participates in the activation of inflammasomes and pyroptosis. Meanwhile, ubiquitination strictly regulates inflammatory responses. However, how ubiquitination regulates Gasdermin D activity is not well understood. In this study, we show that pyroptosis triggered by Gasdermin D...

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Autores principales: Shi, Yuhua, Yang, Yang, Xu, Weilv, Shi, Dongyun, Xu, Wei, Fu, Xinyu, Lv, Qian, Xia, Jie, Shi, Fushan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814081/
https://www.ncbi.nlm.nih.gov/pubmed/35115505
http://dx.doi.org/10.1038/s41419-022-04553-x
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author Shi, Yuhua
Yang, Yang
Xu, Weilv
Shi, Dongyun
Xu, Wei
Fu, Xinyu
Lv, Qian
Xia, Jie
Shi, Fushan
author_facet Shi, Yuhua
Yang, Yang
Xu, Weilv
Shi, Dongyun
Xu, Wei
Fu, Xinyu
Lv, Qian
Xia, Jie
Shi, Fushan
author_sort Shi, Yuhua
collection PubMed
description Gasdermin D (GSDMD) participates in the activation of inflammasomes and pyroptosis. Meanwhile, ubiquitination strictly regulates inflammatory responses. However, how ubiquitination regulates Gasdermin D activity is not well understood. In this study, we show that pyroptosis triggered by Gasdermin D is regulated through ubiquitination. Specifically, SYVN1, an E3 ubiquitin ligase of gasdermin D, promotes GSDMD-mediated pyroptosis. SYVN1 deficiency inhibits pyroptosis and subsequent LDH release and PI uptake. SYVN1 directly interacts with GSDMD, and mediates K27-linked polyubiquitination of GSDMD on K203 and K204 residues, promoting GSDMD-induced pyroptotic cell death. Thus, our findings revealed the essential role of SYVN1 in GSDMD-mediated pyroptosis. Overall, GSDMD ubiquitination is a potential therapeutic module for inflammatory diseases.
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spelling pubmed-88140812022-02-16 E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis Shi, Yuhua Yang, Yang Xu, Weilv Shi, Dongyun Xu, Wei Fu, Xinyu Lv, Qian Xia, Jie Shi, Fushan Cell Death Dis Article Gasdermin D (GSDMD) participates in the activation of inflammasomes and pyroptosis. Meanwhile, ubiquitination strictly regulates inflammatory responses. However, how ubiquitination regulates Gasdermin D activity is not well understood. In this study, we show that pyroptosis triggered by Gasdermin D is regulated through ubiquitination. Specifically, SYVN1, an E3 ubiquitin ligase of gasdermin D, promotes GSDMD-mediated pyroptosis. SYVN1 deficiency inhibits pyroptosis and subsequent LDH release and PI uptake. SYVN1 directly interacts with GSDMD, and mediates K27-linked polyubiquitination of GSDMD on K203 and K204 residues, promoting GSDMD-induced pyroptotic cell death. Thus, our findings revealed the essential role of SYVN1 in GSDMD-mediated pyroptosis. Overall, GSDMD ubiquitination is a potential therapeutic module for inflammatory diseases. Nature Publishing Group UK 2022-02-03 /pmc/articles/PMC8814081/ /pubmed/35115505 http://dx.doi.org/10.1038/s41419-022-04553-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Shi, Yuhua
Yang, Yang
Xu, Weilv
Shi, Dongyun
Xu, Wei
Fu, Xinyu
Lv, Qian
Xia, Jie
Shi, Fushan
E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis
title E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis
title_full E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis
title_fullStr E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis
title_full_unstemmed E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis
title_short E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis
title_sort e3 ubiquitin ligase syvn1 is a key positive regulator for gsdmd-mediated pyroptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814081/
https://www.ncbi.nlm.nih.gov/pubmed/35115505
http://dx.doi.org/10.1038/s41419-022-04553-x
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