ArticleThe Journal of biological chemistry2011
Anti-Ro52 autoantibodies from patients with Sjögren's syndrome inhibit the Ro52 E3 ligase activity by blocking the E3/E2 interface.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 91 citations in OpenAlex.
- The presence of anti-Ro52/SSA antibodies may predict concomitant pulmonary hypertension and poorer survival in patients with connective tissue disease-associated interstitial lung disease.Clinical rheumatology · 2026Observational
- Tripartite motif containing 21 autoimmunity primes CD8Arthritis research & therapy · 2026Article
- Dysregulation of the DNA repair‑immune axis: Targeted therapeutic strategies for autoimmune diseases (Review).International journal of molecular medicine · 2026Review
- Autoantibody internalization in myositis skeletal muscle: Emerging evidence, mechanistic insights, and therapeutic relevance.Autoimmunity reviews · 2026Review
- Sex differences in primary Sjögren's disease: prognostic impact on mortality and cancer.Biology of sex differences · 2026Observational
- Isolated Anti-SS-A Antibody Seropositivity as a Poor Prognostic Factor in Systemic Sclerosis: Insights From a Cohort of 307 Cases.The Journal of dermatology · 2026Article
- A cross-sectional observational study of patients with sicca with salivary autoantibodies defines a potential new phenotype of Sjögren's disease.Annals of the rheumatic diseases · 2025Observational
- Anti- Melanoma Differentiation-Associated Gene 5 Antibody Positive Dermatomyositis: Recent Progress in Pathophysiology and Treatment.Current rheumatology reports · 2025Review
- Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- TRIM21 regulation of IRF-mediated type I interferon signaling in systemic autoimmune diseases.Frontiers in immunology · 2025Review
- Clinical features of patients with systemic sclerosis positive for anti-SS-A antibody: a cohort study of 156 patients.Arthritis research & therapy · 2024Article
- Autoantibodies against the melanoma differentiation-associated protein 5 in patients with dermatomyositis target the helicase domains.Rheumatology (Oxford, England) · 2024Article
- Autoimmune diseases: targets, biology, and drug discovery.Acta pharmacologica Sinica · 2024Review
- TLR7 activation of age-associated B cells mediates disease in a mouse model of primary Sjögren's disease.Journal of leukocyte biology · 2024Article
- Roles of TRIM21/Ro52 in connective tissue disease-associated interstitial lung diseases.Frontiers in immunology · 2024Review
- Dissociating Autoantibody Responses against Ro52 Antigen in Patients with Anti-Synthetase or Anti-MDA5 Antibodies.Diagnostics (Basel, Switzerland) · 2023Article
- 14-3-3η Proteins as a Diagnostic Marker, Disease Activation Indicator, and Lymphoma Predictor in Patients with Primary Sjögren Syndrome.Archives of Iranian medicine · 2023Article
- Anti-Ro52 positivity is associated with progressive interstitial lung disease in systemic sclerosis-an exploratory study.Arthritis research & therapy · 2023Article
- UBE2E2 enhances Snail-mediated epithelial-mesenchymal transition and Nrf2-mediated antioxidant activity in ovarian cancer.Cell death & disease · 2023Article
- Clinical characteristics of idiopathic interstitial pneumonias with anti-Ro52/tripartite motif-containing 21 antibodies.Scientific reports · 2022Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ro52 (TRIM21) is an E3 ligase of the tripartite motif family that negatively regulates proinflammatory cytokine production by ubiquitinating transcription factors of the interferon regulatory factor family. Autoantibodies to Ro52 are present in patients with lupus and Sjögren's syndrome, but it is not known if these autoantibodies affect the function of Ro52. To address this question, the requirements for Ro52 E3 ligase activity were first analyzed in detail. Scanning a panel of E2 ubiquitin-conjugating enzymes, we found that UBE2D1-4 and UBE2E1-2 supported the E3 ligase activity of Ro52 and that the E3 ligase activity of Ro52 was dependent on its RING domain. We also found that the N-terminal extensions in the class III E2 enzymes affected their interaction with Ro52. Although the N-terminal extension in UBE2E3 made this E2 enzyme unable to function together with Ro52, the N-terminal extensions in UBE2E1 and UBE2E2 allowed for a functional interaction with Ro52. Anti-Ro52-positive patient sera and affinity-purified anti-RING domain autoantibodies inhibited the E3 activity of Ro52 in ubiquitination assays. Using NMR, limited proteolysis, ELISA, and Ro52 mutants, we mapped the interactions between Ro52, UBE2E1, and anti-Ro52 autoantibodies. We found that anti-Ro52 autoantibodies inhibited the E3 ligase activity of Ro52 by sterically blocking the E2/E3 interaction between Ro52 and UBE2E1. Our data suggest that anti-Ro52 autoantibodies binding the RING domain of Ro52 may be actively involved in the pathogenesis of rheumatic autoimmune disease by inhibiting Ro52-mediated ubiquitination.
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