ArticleNature immunology2020
Two distinct ubiquitin-binding motifs in A20 mediate its anti-inflammatory and cell-protective activities.
Article in Nature immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 85 citations in OpenAlex.
- Targeting USP47 reprograms macrophage polarization to ameliorate septic peritonitis and promote cutaneous wound healing.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Iron, Copper, and Zinc Dyshomeostasis in Cardiovascular and Cerebrovascular Diseases: Redox Mechanisms, Evidence Levels, and Translational Prospects.International journal of molecular sciences · 2026Review
- Autosomal recessive A20 zinc finger 7 mutation is associated with early-onset lupus-like disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Limitations of EBV transformed human Raji B cells as a model for measuring canonical NF-κB activation.bioRxiv : the preprint server for biology · 2026Article
- How I Treat: Haploinsufficiency of A20.Journal of human immunity · 2026Review
- Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Five children with haploinsufficiency of A20 caused by heterozygous mutations in theFrontiers in immunology · 2026Article
- Unrestrained MyD88 Signaling in A20-Deficient Keratinocytes Triggers T-Cell-Dependent Psoriatic Arthritis-Like Disease.The Journal of investigative dermatology · 2025Article
- Base-editing a single missense mutation in A20 enhances CAR-T cell efficacy.bioRxiv : the preprint server for biology · 2025Article
- Spatiotemporal Regulation of STING Activity by Linear Ubiquitination Governs Antiviral Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The pathogenesis, clinical presentations and treatment of monogenic systemic vasculitis.Nature reviews. Rheumatology · 2025Review
- ZSH-2208: A novel retinoid with potent anti-tumour effects on ESCC stem cells via RARγ-TNFAIP3 axis.Clinical and translational medicine · 2025Article
- A20 intrinsically influences human effector T-cell survival and function by regulating both NF-κB and JNK signaling.European journal of immunology · 2024Article
- Genetic Mutations Associated With TNFAIP3 (A20) Haploinsufficiency and Their Impact on Inflammatory Diseases.International journal of molecular sciences · 2024Review
- Inhibition of NLRP3 inflammasome activation by A20 through modulation of NEK7.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A20 in Kidney Transplantation and Autoimmunity.International journal of molecular sciences · 2024Review
- Ubiquitous regulation of cerebrovascular diseases by ubiquitin-modifying enzymes.Clinical and translational medicine · 2024Review
- N4BP1 functions as a dimerization-dependent linear ubiquitin reader which regulates TNF signalling.Cell death discovery · 2024Article
- The Complexity of Being A20: From Biological Functions to Genetic Associations.Journal of clinical immunology · 2024Review
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Authors and funding
20 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein ubiquitination regulates protein stability and modulates the composition of signaling complexes. A20 is a negative regulator of inflammatory signaling, but the molecular mechanisms involved are ill understood. Here, we generated Tnfaip3 gene-targeted A20 mutant mice bearing inactivating mutations in the zinc finger 7 (ZnF7) and ZnF4 ubiquitin-binding domains, revealing that binding to polyubiquitin is essential for A20 to suppress inflammatory disease. We demonstrate that a functional ZnF7 domain was required for recruiting A20 to the tumor necrosis factor receptor 1 (TNFR1) signaling complex and to suppress inflammatory signaling and cell death. The combined inactivation of ZnF4 and ZnF7 phenocopied the postnatal lethality and severe multiorgan inflammation of A20-deficient mice. Conditional tissue-specific expression of mutant A20 further revealed the key role of ubiquitin-binding in myeloid and intestinal epithelial cells. Collectively, these results demonstrate that the anti-inflammatory and cytoprotective functions of A20 are largely dependent on its ubiquitin-binding properties.
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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.