ArticleThe EMBO journal2024
Shared and distinct mechanisms of UBA1 inactivation across different diseases.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- American College of Rheumatology Guidance Statement for Diagnosis and Management of VEXAS Developed by the International VEXAS Working Group Expert Panel.Arthritis & rheumatology (Hoboken, N.J.) · 2026Guideline
- Myelodysplasia in VEXAS syndrome.Blood advances · 2026Review
- SomaticBlood neoplasia · 2026Article
- Macrocytosis combined with monoclonal gammopathy identifies patients carrying VEXAS-linkedHemaSphere · 2026Article
- Disruption of the ubiquitin-mediated proteolysis pathway: a study of seed aging in Saposhnikovia divaricata caused by UBC1 gene family suppression.BMC plant biology · 2026Article
- Cell autonomous inflammation in VEXAS is mediated by cGAS-STING.bioRxiv : the preprint server for biology · 2026Article
- VEXAS syndrome.Nature reviews. Disease primers · 2026Review
- UBA6 specificity for ubiquitin E2 conjugating enzymes reveals a priority mechanism of BIRC6.Nature structural & molecular biology · 2026Article
- Clinical-Pathological Conference Series from the Medical University of Graz : Case No 183: A 57-year-old farmer with fever, cough, maculopapular rash and bicytopenia.Wiener klinische Wochenschrift · 2026Article
- Disease Trajectories and Glucocorticoid Exposure in VEXAS Syndrome Treated with Cytokine-Directed Therapies.Annals of the rheumatic diseases · 2026Article
- Comparative Efficacy and Safety of Anakinra and Canakinumab in Patients With VEXAS Syndrome: An International Multicenter Study.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Cul5: immune cell function and therapeutic potential.Frontiers in immunology · 2026Review
- Mapping VEXAS-associated and rare UBA1 variants in the United Kingdom: Insights from patient cohorts and the general population.British journal of haematology · 2026Article
- Human clearance systems have a layered architecture across tissues and cell types that supports varied proteome compositions.Autophagy · 2026Article
- UBA1 as a proteostasis-innate immunity checkpoint: lessons from vexas syndrome and therapeutic implications.Frontiers in immunology · 2026Review
- Clinical Manifestations of VEXAS Syndrome Across a Broad Spectrum of UBA1 Mutation Burden.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Distinct characteristics of VEXAS-causative UBA1 M41 and recurrent functional non-M41 mutations.Leukemia · 2025Article
- Coexistence of VEXAS Syndrome and Chronic Hepatitis B Virus Infection: a Case Report and Literature Review.Clinical reviews in allergy & immunology · 2025Review
- Expert Perspective: Hematologic Malignancies and Vasculitis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Review
- Rapid clinical deployment of UBA1 testing in patients with VEXAS syndrome.American journal of clinical pathology · 2025Article
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Most cellular ubiquitin signaling is initiated by UBA1, which activates and transfers ubiquitin to tens of E2 enzymes. Clonally acquired UBA1 missense mutations cause an inflammatory-hematologic overlap disease called VEXAS (vacuoles, E1, X-linked, autoinflammatory, somatic) syndrome. Despite extensive clinical investigation into this lethal disease, little is known about the underlying molecular mechanisms. Here, by dissecting VEXAS-causing UBA1 mutations, we discovered that p.Met41 mutations alter cytoplasmic isoform expression, whereas other mutations reduce catalytic activity of nuclear and cytoplasmic isoforms by diverse mechanisms, including aberrant oxyester formation. Strikingly, non-p.Met41 mutations most prominently affect transthioesterification, revealing ubiquitin transfer to cytoplasmic E2 enzymes as a shared property of pathogenesis amongst different VEXAS syndrome genotypes. A similar E2 charging bottleneck exists in some lung cancer-associated UBA1 mutations, but not in spinal muscular atrophy-causing UBA1 mutations, which instead, render UBA1 thermolabile. Collectively, our results highlight the precision of conformational changes required for faithful ubiquitin transfer, define distinct and shared mechanisms of UBA1 inactivation in diverse diseases, and suggest that specific E1-E2 modules control different aspects of tissue differentiation and maintenance.
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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.