ArticleThe Journal of clinical investigation2019
USP16-mediated deubiquitination of calcineurin A controls peripheral T cell maintenance.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- Palmitic Acid Inhibits the Proliferation and Hypertrophy of Antler Chondrocytes by Disrupting Mitochondria-Associated Endoplasmic Reticulum Membrane Function.Antioxidants (Basel, Switzerland) · 2026Article
- USP16 drives psoriasis progression by deubiquitinating and stabilizing NLRP3 in keratinocytes.JCI insight · 2026Article
- Mechanism of USP21 autoinhibition and histone H2AK119 deubiquitination.Science advances · 2025Article
- SMURF1 mediates damaged lysosomal homeostasis by ubiquitinating PPP3CB to promote the activation of TFEB.Autophagy · 2025Article
- Bioinformatics‑Based Analysis Reveals Diagnostic Biomarkers and Immune Landscape in Atopic Dermatitis.Clinical, cosmetic and investigational dermatology · 2025Article
- IFI27 inhibits HIV-1 replication by degrading Gag protein through the ubiquitin-proteasome pathway.Journal of virology · 2024Article
- Trim21-mediated CCT2 ubiquitination suppresses malignant progression and promotes CD4Cell death & disease · 2024Article
- Deubiquitinases in muscle physiology and disorders.Biochemical Society transactions · 2024Review
- SMURF1 controls the PPP3/calcineurin complex and TFEB at a regulatory node for lysosomal biogenesis.Autophagy · 2024Article
- Roles of ubiquitin-specific proteases in inflammatory diseases.Frontiers in immunology · 2024Review
- Goliath induces inflammation in obese mice by linking fatty acid β-oxidation to glycolysis.EMBO reports · 2023Article
- TRABID overexpression enables synthetic lethality to PARP inhibitor via prolonging 53BP1 retention at double-strand breaks.Nature communications · 2023Article
- Review
- The prognostic value of whole-genome DNA methylation in response to Leflunomide in patients with Rheumatoid Arthritis.Frontiers in immunology · 2023Article
- USP16-mediated histone H2A lysine-119 deubiquitination during oocyte maturation is a prerequisite for zygotic genome activation.Nucleic acids research · 2022Article
- Yeast as a Model to Find New Drugs and Drug Targets forInternational journal of molecular sciences · 2022Review
- Modulating the Ubiquitin-Proteasome System: A Therapeutic Strategy for Autoimmune Diseases.Cells · 2022Review
- Article
- Brain Epitranscriptomic Analysis Revealed Altered A-to-I RNA Editing in Septic Patients.Frontiers in genetics · 2022Article
- Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calcineurin acts as a calcium-activated phosphatase that dephosphorylates various substrates, including members of the nuclear factor of activated T cells (NFAT) family, to trigger their nuclear translocation and transcriptional activity. However, the detailed mechanism regulating the recruitment of NFATs to calcineurin remains poorly understood. Here, we report that calcineurin A (CNA), encoded by PPP3CB or PPP3CC, is constitutively ubiquitinated on lysine 327, and this polyubiquitin chain is rapidly removed by ubiquitin carboxyl-terminal hydrolase 16 (USP16) in response to intracellular calcium stimulation. The K29-linked ubiquitination of CNA impairs NFAT recruitment and transcription of NFAT-targeted genes. USP16 deficiency prevents calcium-triggered deubiquitination of CNA in a manner consistent with defective maintenance and proliferation of peripheral T cells. T cell-specific USP16 knockout mice exhibit reduced severity of experimental autoimmune encephalitis and inflammatory bowel disease. Our data reveal the physiological function of CNA ubiquitination and its deubiquitinase USP16 in peripheral T cells. Notably, our results highlight a critical mechanism for the regulation of calcineurin activity and a novel immunosuppressive drug target for the treatment of autoimmune diseases.
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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 Socratic graph.