The role of ubiquitinase in B cell development and function

Zhang, Tong; Sun, Jian‐Xuan; Cheng, Jiali; Yin, Wei; Li, Jingwen; Miller, Heather; Herrada, Andrés A.; Gu, Heng; Song, Haiqu; Chen, Yan; Gong, Quan; Liu, Chaohong

doi:10.1002/jlb.1mr0720-185rr

Cited by 4 publications

(6 citation statements)

References 120 publications

(213 reference statements)

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“…Furthermore, by analysing the DEGs of immune cells in SMGs and PBMCs of patients with IgG4-RD, we found that UBC , TOMM7 , RACK1 , NACA and UBA52 were the shared genes (figure 5H). UBC and UBA52 are ubiquitination-related genes and protein ubiquitination plays a crucial role in T-cell and B-cell development and function processes 20 21…”

Section: Resultsmentioning

confidence: 99%

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Wang

Feng

et al. 2023

Ann Rheum Dis

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ObjectivesThe aim of this study is to profile the transcriptional landscapes of affected tissues and peripheral blood mononuclear cells (PBMCs) at the single-cell level in IgG4-related disease (IgG4-RD). Identifying the cell populations and crosstalk between immune cells and non-immune cells will assist us in understanding the aetiology of IgG4-RD.MethodsWe performed single-cell RNA sequencing analysis on submandibular glands (SMGs) and PBMCs from patients with IgG4-RD and matched controls. Additionally, bulk RNA sequencing of PBMCs was used to construct the immune repertoire. Furthermore, multiplex immunofluorescence staining was performed to validate the transcriptomic results.ResultsWe identified three novel subsets of tissue-resident immune cells in the SMGs of patients with IgG4-RD.TOP2A_B cells andTOP2A_T cells had stemness signatures, and trajectory analysis showed thatTOP2A_B cells may differentiate into IgG4+plasma cells and thatTOP2A_T cells may differentiate into T follicular helper (Tfh) cells.ICOS_PD-1_B cells with Tfh-like characteristics appeared to be an intermediate state in the differentiation from B cells to IgG4+plasma cells. The cellular communication patterns within immune cells and between immune cells and non-immune cells were altered in IgG4-RD compared with controls. Consistently, infection-related pathways were shared in B cells and T cells from SMGs and PBMCs. Furthermore, immune clonotype analysis of PBMC samples showed the complementary determining region 3 amino acid CQQSYSTPYTF was expanded in patients with IgG4-RD.ConclusionOur data revealed the cellular and molecular changes at the single-cell resolution of IgG4-RD and provide valuable insights into the aetiology and novel therapeutic targets of the autoimmune disease.

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Section: Resultsmentioning

confidence: 99%

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Wang

Feng

et al. 2023

Ann Rheum Dis

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“…E3 Ub ligase Hrd1 mediates the downregulation of pre‐BCR through ubiquitination and promotes the maturation of pre‐B cells. 878 …”

Section: Ubiquitinationmentioning

confidence: 99%

“…E3 Ub ligase Hrd1 mediates the downregulation of pre-BCR through ubiquitination and promotes the maturation of pre-B cells. 878 Viruses can escape from immunity by degrading target proteins. For example, the CoV nucleocapsid (N) protein of SADS-CoV interacts with RIG-I and promotes its K27-, K48-, and K63-linked ubiquitination to induce RIG-I degradation, which further inhibits the host IFNβ response.…”

Section: Ubiquitination In Immune Regulationmentioning

confidence: 99%

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Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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“…Ubiquitination and deubiquitination are also important processes in the regulation of B cell activation, proliferation, and apoptosis during development and their functional diversification and activation in innate and humoral immune responses 25 . A systems-wide analysis of B cell receptor signalosomes has identified USP8 as an interacting component upon stimulation 26 .…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin-specific protease 8 controls B-cell proteostasis and survival representing a target in multiple myeloma

Dufner,

Thery,

Monaco

et al. 2024

Preprint

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Ubiquitin-specific protease 8 exerts multiple cellular functions and was identified as a potential target in a multiple myeloma vulnerability screen. Here we characterized the function of USP8 in B cells and multiple myeloma, and analyzed its impact on the global and ubiquitin-modified proteome.Usp8deletion in mice starting at the the pre-B cell stage caused a partial block in B cell development favoring immature and innate-like B cells, as well as germinal center and plasma cells. This was accompanied by elevated immune-responses and Roquin depletion. Accordingly, correlation analyses in multiple myeloma patients revealed that low USP8 expression at diagnosis correlates with decreased survival. B cells expressing catalytically inactive USP8 accumulate protein modified with mixed ubiquitin/NEDD8 chains as hallmarks of proteotoxic stress, which we identified as favored USP8 substrates. USP8 knockdown reduced survival of bortezomib-resistant multiple myeloma cells in a lysosomal dysfunction-dependent manner. In contrast, the inhibitor DUB-IN-2 resensitized bortezomib-resistant multiple myeloma cells to treatment in a bortezomib-synergistic manner. Hence, our analyses uncovered the therapeutic potential of USP8 inhibition and of DUB-IN-2 in multiple myeloma.

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The role of ubiquitinase in B cell development and function

Cited by 4 publications

References 120 publications

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Ubiquitin-specific protease 8 controls B-cell proteostasis and survival representing a target in multiple myeloma

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