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USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID

Activation-induced cytidine deaminase (AID) initiates class-switch recombination and somatic hypermutation (SHM) in antibody genes. Protein expression and activity are tightly controlled by various mechanisms. However, it remains unknown whether a signal from the extracellular environment directly a...

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Autores principales: Luo, Yuewen, Zhang, Xiantao, Chen, Ran, Li, Rong, Liu, Yang, Zhang, Junsong, liu, Qin, Si, Meijun, Liu, Jun, Wu, Bolin, Wang, Xuemei, Wu, Shijian, Zhang, Yiwen, Zhang, Xu, Guo, Deyin, He, Xin, Pan, Ting, Zhang, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724756/
https://www.ncbi.nlm.nih.gov/pubmed/34983926
http://dx.doi.org/10.1038/s41392-021-00858-z
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author Luo, Yuewen
Zhang, Xiantao
Chen, Ran
Li, Rong
Liu, Yang
Zhang, Junsong
liu, Qin
Si, Meijun
Liu, Jun
Wu, Bolin
Wang, Xuemei
Wu, Shijian
Zhang, Yiwen
Zhang, Xu
Guo, Deyin
He, Xin
Pan, Ting
Zhang, Hui
author_facet Luo, Yuewen
Zhang, Xiantao
Chen, Ran
Li, Rong
Liu, Yang
Zhang, Junsong
liu, Qin
Si, Meijun
Liu, Jun
Wu, Bolin
Wang, Xuemei
Wu, Shijian
Zhang, Yiwen
Zhang, Xu
Guo, Deyin
He, Xin
Pan, Ting
Zhang, Hui
author_sort Luo, Yuewen
collection PubMed
description Activation-induced cytidine deaminase (AID) initiates class-switch recombination and somatic hypermutation (SHM) in antibody genes. Protein expression and activity are tightly controlled by various mechanisms. However, it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it works. Here, we demonstrated that a deubiquitinase USP10, which specifically stabilizes nuclear AID protein, can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS domain. Interestingly, the signals from BCR and TLR1/2 synergistically promoted this phosphorylation. The deficiency of USP10 in B cells significantly decreased AID protein levels, subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or human immunodeficiency virus type 1 (HIV-1) nanoparticle vaccines. Collectively, we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity. Its manipulation could be used for the development of vaccines and adjuvants.
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spelling pubmed-87247562022-01-04 USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID Luo, Yuewen Zhang, Xiantao Chen, Ran Li, Rong Liu, Yang Zhang, Junsong liu, Qin Si, Meijun Liu, Jun Wu, Bolin Wang, Xuemei Wu, Shijian Zhang, Yiwen Zhang, Xu Guo, Deyin He, Xin Pan, Ting Zhang, Hui Signal Transduct Target Ther Article Activation-induced cytidine deaminase (AID) initiates class-switch recombination and somatic hypermutation (SHM) in antibody genes. Protein expression and activity are tightly controlled by various mechanisms. However, it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it works. Here, we demonstrated that a deubiquitinase USP10, which specifically stabilizes nuclear AID protein, can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS domain. Interestingly, the signals from BCR and TLR1/2 synergistically promoted this phosphorylation. The deficiency of USP10 in B cells significantly decreased AID protein levels, subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or human immunodeficiency virus type 1 (HIV-1) nanoparticle vaccines. Collectively, we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity. Its manipulation could be used for the development of vaccines and adjuvants. Nature Publishing Group UK 2022-01-04 /pmc/articles/PMC8724756/ /pubmed/34983926 http://dx.doi.org/10.1038/s41392-021-00858-z 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
Luo, Yuewen
Zhang, Xiantao
Chen, Ran
Li, Rong
Liu, Yang
Zhang, Junsong
liu, Qin
Si, Meijun
Liu, Jun
Wu, Bolin
Wang, Xuemei
Wu, Shijian
Zhang, Yiwen
Zhang, Xu
Guo, Deyin
He, Xin
Pan, Ting
Zhang, Hui
USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID
title USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID
title_full USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID
title_fullStr USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID
title_full_unstemmed USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID
title_short USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID
title_sort usp10 regulates b cell response to sars-cov-2 or hiv-1 nanoparticle vaccines through deubiquitinating aid
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724756/
https://www.ncbi.nlm.nih.gov/pubmed/34983926
http://dx.doi.org/10.1038/s41392-021-00858-z
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