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USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses
Toll-like receptors (TLRs) are involved in the sensing of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), flagellin, unmethylated double-stranded DNA (CpG), single-stranded RNA (ssRNA) and lipoproteins. Myeloid differentiation primary response protein 88 (MyD88) is a...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412818/ https://www.ncbi.nlm.nih.gov/pubmed/36032091 http://dx.doi.org/10.3389/fimmu.2022.900243 |
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author | Zhang, Na Wang, Fei Zhang, Gaomeng Zhang, Qi Liu, Yuhong Wang, Qiao Elsharkawy, Mohamed Shafey Zheng, Maiqing Wen, Jie Zhao, Guiping Li, Qinghe |
author_facet | Zhang, Na Wang, Fei Zhang, Gaomeng Zhang, Qi Liu, Yuhong Wang, Qiao Elsharkawy, Mohamed Shafey Zheng, Maiqing Wen, Jie Zhao, Guiping Li, Qinghe |
author_sort | Zhang, Na |
collection | PubMed |
description | Toll-like receptors (TLRs) are involved in the sensing of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), flagellin, unmethylated double-stranded DNA (CpG), single-stranded RNA (ssRNA) and lipoproteins. Myeloid differentiation primary response protein 88 (MyD88) is a canonical adaptor for the Toll-like receptor family which has crucial roles in host defense against infection by microbial pathogens. The dysregulation of MyD88 may also induce autoimmune diseases. Here, we demonstrate that the deubiquitinase USP7 interacts with MyD88 in chicken, with knockdown or overexpression of USP7 leading to the regulation of MyD88 protein in a positive manner. Consequently, USP7 positively regulates the expression of proinflammatory factors upon LPS challenge. Furthermore, we observed USP7-deficient mice to be more susceptible to infection by Salmonella typhimurium. Collectively, our findings demonstrate MyD88 as a bona fide substrate of USP7 and uncover a mechanism by which USP7 regulates innate immune signaling. |
format | Online Article Text |
id | pubmed-9412818 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94128182022-08-27 USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses Zhang, Na Wang, Fei Zhang, Gaomeng Zhang, Qi Liu, Yuhong Wang, Qiao Elsharkawy, Mohamed Shafey Zheng, Maiqing Wen, Jie Zhao, Guiping Li, Qinghe Front Immunol Immunology Toll-like receptors (TLRs) are involved in the sensing of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), flagellin, unmethylated double-stranded DNA (CpG), single-stranded RNA (ssRNA) and lipoproteins. Myeloid differentiation primary response protein 88 (MyD88) is a canonical adaptor for the Toll-like receptor family which has crucial roles in host defense against infection by microbial pathogens. The dysregulation of MyD88 may also induce autoimmune diseases. Here, we demonstrate that the deubiquitinase USP7 interacts with MyD88 in chicken, with knockdown or overexpression of USP7 leading to the regulation of MyD88 protein in a positive manner. Consequently, USP7 positively regulates the expression of proinflammatory factors upon LPS challenge. Furthermore, we observed USP7-deficient mice to be more susceptible to infection by Salmonella typhimurium. Collectively, our findings demonstrate MyD88 as a bona fide substrate of USP7 and uncover a mechanism by which USP7 regulates innate immune signaling. Frontiers Media S.A. 2022-08-12 /pmc/articles/PMC9412818/ /pubmed/36032091 http://dx.doi.org/10.3389/fimmu.2022.900243 Text en Copyright © 2022 Zhang, Wang, Zhang, Zhang, Liu, Wang, Elsharkawy, Zheng, Wen, Zhao and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zhang, Na Wang, Fei Zhang, Gaomeng Zhang, Qi Liu, Yuhong Wang, Qiao Elsharkawy, Mohamed Shafey Zheng, Maiqing Wen, Jie Zhao, Guiping Li, Qinghe USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses |
title | USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses |
title_full | USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses |
title_fullStr | USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses |
title_full_unstemmed | USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses |
title_short | USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses |
title_sort | usp7 promotes deubiquitination and stabilization of myd88 to enhance immune responses |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412818/ https://www.ncbi.nlm.nih.gov/pubmed/36032091 http://dx.doi.org/10.3389/fimmu.2022.900243 |
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