ArticleJournal of immunology (Baltimore, Md. : 1950)2019
UBASH3A Regulates the Synthesis and Dynamics of TCR-CD3 Complexes.
Article in Journal of immunology (Baltimore, Md. : 1950), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Sex-Dimorphic Analyses Identify Novel and Sex-Specific Genetic Associations in Inflammatory Bowel Disease.Inflammatory bowel diseases · 2023Pooled it
- High-Precision Intrinsic Interactome Elucidation of Chimeric Antigen Receptors via Photocatalytic Micromapping (μMap-CAR).Journal of the American Chemical Society · 2026Article
- Associations of non-HLA gene polymorphisms with celiac disease in India.Scientific reports · 2026Article
- Higher Promoter Methylation of the Ubiquitin-Associated and SH3 Domain Containing A (UBASH3A) Gene Is Associated With T-Lymphocyte Ontogeny and Reduced Susceptibility to Early-Onset Sepsis.The Journal of infectious diseases · 2026Article
- SH3 domains selectively activate the PI3 kinase through non-conventional tertiary contacts.Communications biology · 2026Article
- Multiomics Profiling of T-cell Leukemia and Lymphoma Enables Targeted Therapeutic Discovery.Cancer research · 2026Article
- FCRL3 is an immunoregulatory receptor that restrains the activation of human memory T lymphocytes.The Journal of experimental medicine · 2026Article
- Exploring UBASH3A: from immune regulation to autoimmune diseases.Journal of translational medicine · 2025Review
- Multi-omics analysis highlights the link of aging-related cognitive decline with systemic inflammation and alterations of tissue-maintenance.bioRxiv : the preprint server for biology · 2025Article
- STS2 deficiency revives CD8Journal for immunotherapy of cancer · 2025Article
- Copy number normalization distinguishes differential signals driven by copy number differences in ATAC-seq and ChIP-seq.BMC genomics · 2025Article
- Charged substrate treatment enhances T cell mediated cancer immunotherapy.Nature communications · 2025Article
- Roles of TULA-family proteins in T cells and autoimmune diseases.Genes and immunity · 2025Review
- CD6 regulates CD4 T follicular helper cell differentiation and humoral immunity during murine coronavirus infection.Journal of virology · 2025Article
- Identification of New Single Nucleotide Polymorphisms Potentially Related to Small Ruminant Lentivirus Infection Susceptibility in Goats Based on Data Selected from High-Throughput Sequencing.Pathogens (Basel, Switzerland) · 2024Article
- CD6 Regulates CD4 T Follicular Helper Cell Differentiation and Humoral Immunity During Murine Coronavirus Infection.bioRxiv : the preprint server for biology · 2024Article
- Functional selection in SH3-mediated activation of the PI3 kinase.bioRxiv : the preprint server for biology · 2024Article
- Role of Tula-Family Proteins in Cell Signaling and Activation: Advances and Challenges.International journal of molecular sciences · 2024Article
- Differential protein-protein interactions underlie signaling mediated by the TCR and a 4-1BB domain-containing CAR.Science signaling · 2024Article
- The Ubiquitin-Associated and SH3 Domain-Containing Proteins (UBASH3) Family in Mammalian Development and Immune Response.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The TCR-CD3 complex is a multicomponent membrane receptor, the expression of which is tightly regulated in thymocytes, as well as in mature T cells both at steady state and upon stimulation. In this study, we report novel roles for UBASH3A in TCR-CD3 synthesis and turnover. UBASH3A is a negative regulator of T cell function and plays a broad role in autoimmunity. We show that modulation of UBASH3A levels in unstimulated Jurkat cells leads to altered amounts of total cellular CD3 chains and of cell-surface TCR-CD3 complexes; in contrast, UBASH3A does not affect the level of cell-surface CD28, an important T cell costimulatory receptor. Upon TCR engagement, UBASH3A enhances the downmodulation of cell-surface TCR-CD3. Mass spectrometry and protein-protein interaction studies uncover novel associations between UBASH3A and components of several cellular pathways involved in the regulation of TCR-CD3 turnover and dynamics, including endoplasmic reticulum-associated protein degradation, cell motility, endocytosis, and endocytic recycling of membrane receptors. Finally, we demonstrate that the SH3 domain of UBASH3A mediates its binding to CBL-B, an E3 ubiquitin ligase that negatively regulates CD28-mediated signaling and, hence, T cell activation. In summary, this study provides new mechanistic insights into how UBASH3A regulates T cell activation and contributes to autoimmunity. The interaction between UBASH3A and CBL-B may synergistically inhibit T cell function and affect risk for type 1 diabetes, as both genes have been shown to be associated with this autoimmune disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.