ArticleNature immunology2015
The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis.
Article in Nature immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 200 papers, 2 of them syntheses that pooled it.
What it found
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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
200 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Cullin Deneddylation Suppresses the Necroptotic Pathway in Cardiomyocytes.Frontiers in physiology · 2021Pooled it
- Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nature reviews. Drug discovery · 2020Pooled it
- A20 Inhibits IFN-γ Signaling in Hepatocellular Carcinoma Cells by Binding to STAT1, Compromising Anti-Tumor Immunity.Cancer science · 2026Article
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- The ubiquitin-editing enzyme A20 (TNFAIP3): mechanisms of activation, biological function, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Integrated Necroptosis Within Programmed Cell Death in Traumatic Brain Injury.Molecular neurobiology · 2026Review
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Omics in heat stress in poultry: implications for immune responses, proteomic changes, and nutritional strategies.Veterinary research communications · 2026Review
- Inhibiting MDM2 enhances RIPK3-mediated necroptosis and synergizes with immune checkpoint blockade therapy.iScience · 2026Article
- Ubiquitination and autophagy in host-pathogen interactions: from immune surveillance to therapeutic targeting.Nature reviews. Immunology · 2026Review
- Article
- USP13 depletion sensitizes colorectal cancer cells to necroptosis by destabilizing cIAP2 proteins.Cell death and differentiation · 2026Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Targeting ubiquitin-specific peptidase 22 in solid tumours: from ubiquitination to immunotherapy.Frontiers in cell and developmental biology · 2026Review
- Identification of the Role of Necroptosis-Related Genes in the Oxidative Damage of Lens Epithelial Cells and Validation in Ultraviolet B-induced Cataract in Rats.Combinatorial chemistry & high throughput screening · 2026Article
- Article
- A20 restriction of nitric oxide production restores macrophage bioenergetic balance.bioRxiv : the preprint server for biology · 2025Article
- Astrocytic-OTUD7B ameliorates murine experimental autoimmune encephalomyelitis by stabilizing glial fibrillary acidic protein and preventing inflammation.Nature communications · 2025Article
- Base-editing a single missense mutation in A20 enhances CAR-T cell efficacy.bioRxiv : the preprint server for biology · 2025Article
- A20's linear ubiquitin-binding motif restrains pathogenic activation of Th17 cells and IL-22-driven enteritis.The Journal of clinical investigation · 2025Article
140 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
17 authors.
Funding
Abstract
A20 is an anti-inflammatory protein linked to multiple human diseases; however, the mechanisms by which A20 prevents inflammatory disease are incompletely defined. We found that A20-deficient T cells and fibroblasts were susceptible to caspase-independent and kinase RIPK3-dependent necroptosis. Global deficiency in RIPK3 significantly restored the survival of A20-deficient mice. A20-deficient cells exhibited exaggerated formation of RIPK1-RIPK3 complexes. RIPK3 underwent physiological ubiquitination at Lys5 (K5), and this ubiquitination event supported the formation of RIPK1-RIPK3 complexes. Both the ubiquitination of RIPK3 and formation of the RIPK1-RIPK3 complex required the catalytic cysteine of A20's deubiquitinating motif. Our studies link A20 and the ubiquitination of RIPK3 to necroptotic cell death and suggest additional mechanisms by which A20 might prevent inflammatory disease.
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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.