ArticleProceedings of the National Academy of Sciences of the United States of America2016
Usp12 stabilizes the T-cell receptor complex at the cell surface during signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome.Chemical reviews · 2025Review
- Unravelling the role of ubiquitin-specific proteases in breast carcinoma: insights into tumour progression and immune microenvironment modulation.World journal of surgical oncology · 2025Review
- Proximity-dependent biotinylation reveals an interaction between ubiquitin-specific peptidase 46 and centrosome-related proteins.FEBS open bio · 2025Article
- Usp25-Erlin1/2 activity limits cholesterol flux to restrict virus infection.Developmental cell · 2023Article
- Spotlights on ubiquitin-specific protease 12 (USP12) in diseases: from multifaceted roles to pathophysiological mechanisms.Journal of translational medicine · 2023Review
- USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.PLoS pathogens · 2023Article
- Viral subversion of selective autophagy is critical for biogenesis of virus replication organelles.Nature communications · 2023Article
- Deubiquitinating Enzyme USP12 Regulates the Pro-Apoptosis Protein Bax.International journal of molecular sciences · 2022Article
- The DUB Club: Deubiquitinating Enzymes and Neurodevelopmental Disorders.Biological psychiatry · 2022Review
- Adoptive transfer of IL-4 reprogrammed Tc17 cells elicits anti-tumour immunity through functional plasticity.Immunology · 2022Article
- Recycling and Reshaping-E3 Ligases and DUBs in the Initiation of T Cell Receptor-Mediated Signaling and Response.International journal of molecular sciences · 2022Review
- Deubiquitylase USP12 induces pro-survival autophagy and bortezomib resistance in multiple myeloma by stabilizing HMGB1.Oncogene · 2022Article
- Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy.International journal of molecular sciences · 2021Review
- USP12 promotes CD4Cell death and differentiation · 2021Article
- UAF1 deubiquitinase complexes facilitate NLRP3 inflammasome activation by promoting NLRP3 expression.Nature communications · 2020Article
- Lyn kinase regulates egress of flaviviruses in autophagosome-derived organelles.Nature communications · 2020Article
- The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases.International journal of molecular sciences · 2020Review
- Monitoring protein communities and their responses to therapeutics.Nature reviews. Drug discovery · 2020Review
- Coupling Conjugation and Deconjugation Activities to Achieve Cellular Ubiquitin Dynamics.Trends in biochemical sciences · 2020Review
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Posttranslational modifications are central to the spatial and temporal regulation of protein function. Among others, phosphorylation and ubiquitylation are known to regulate proximal T-cell receptor (TCR) signaling. Here we used a systematic and unbiased approach to uncover deubiquitylating enzymes (DUBs) that participate during TCR signaling in primary mouse T lymphocytes. Using a C-terminally modified vinyl methyl ester variant of ubiquitin (HA-Ub-VME), we captured DUBs that are differentially recruited to the cytosol on TCR activation. We identified ubiquitin-specific peptidase (Usp) 12 and Usp46, which had not been previously described in this pathway. Stimulation with anti-CD3 resulted in phosphorylation and time-dependent translocation of Usp12 from the nucleus to the cytosol. Usp12(-/-) Jurkat cells displayed defective NFκB, NFAT, and MAPK activities owing to attenuated surface expression of TCR, which were rescued on reconstitution of wild type Usp12. Proximity-based labeling with BirA-Usp12 revealed several TCR adaptor proteins acting as interactors in stimulated cells, of which LAT and Trat1 displayed reduced expression in Usp12(-/-) cells. We demonstrate that Usp12 deubiquitylates and prevents lysosomal degradation of LAT and Trat1 to maintain the proximal TCR complex for the duration of signaling. Our approach benefits from the use of activity-based probes in primary cells without any previous genome modification, and underscores the importance of ubiquitin-mediated regulation to refine signaling cascades.
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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.