ArticleProceedings of the National Academy of Sciences of the United States of America2024
Inhibition of NLRP3 inflammasome activation by A20 through modulation of NEK7.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The impact of post-translational modifications and subcellular localization on NLRP3 inflammasome activation: A systematic review.Cell communication and signaling : CCS · 2025Pooled it
- The ubiquitin-editing enzyme A20 (TNFAIP3): mechanisms of activation, biological function, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Pharmaceutical therapies for pyroptosis in lung injury.Inflammopharmacology · 2026Review
- Reprogramming of the hepatic ubiquitin‑immune axis: A unifying mechanism in liver disease progression (Review).Molecular medicine reports · 2026Review
- Article
- Molecular mechanisms of NLRP3 inflammasome activation.Experimental & molecular medicine · 2026Review
- The Crohn's disease-related RNF123 prevents NLRP3 inflammasome assembly by catalyzing unanchored K63-linked ubiquitination on NEK7.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A20 Facilitates Oxaliplatin Sensitivity in Colorectal Cancer Through Monoubiquitylation of IKK-β.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Deciphering the NEK7-NLRP3 inflammasome assembly: from conformational activation to allosteric drug discovery.Frontiers in immunology · 2026Review
- Hyperglycemic microenvironment-driven periodontal tissue defects: pathogenic mechanisms and therapeutic advances.Frontiers in dental medicine · 2026Review
- Targeting pyroptosis in periodontitis: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Specific inhibition of NLRP3 inflammasome by a Smurf1 inhibitorOpen medicine (Warsaw, Poland) · 2026Article
- Global trends and mechanistic insights into A20 (TNFAIP3) in autoimmunity and inflammation.American journal of translational research · 2026Review
- A20 Attenuates Inflammatory Injury in Bovine Endometrial Epithelial Cells Through Autophagy-Mediated NLRP3 Inflammasome Inactivation.Animals : an open access journal from MDPI · 2025Article
- Transition of cellular senescence to pyroptosis mediates recurrence of small cell lung cancer after chemotherapy.Science advances · 2025Article
- Review
- Updated insights into the molecular networks for NLRP3 inflammasome activation.Cellular & molecular immunology · 2025Review
- A20 attenuates oxidized self-DNA-mediated inflammation in acute kidney injury.Signal transduction and targeted therapy · 2025Article
- Ubiquitination in macrophage plasticity: from inflammatory to immunometabolic pathways.Frontiers in immunology · 2025Review
- 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
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
The NLRP3 inflammasome, a pivotal component of innate immunity, has been implicated in various inflammatory disorders. The ubiquitin-editing enzyme A20 is well known to regulate inflammation and maintain homeostasis. However, the precise molecular mechanisms by which A20 modulates the NLRP3 inflammasome remain poorly understood. Here, our study revealed that macrophages deficient in A20 exhibit increased protein abundance and elevated mRNA level of NIMA-related kinase 7 (NEK7). Importantly, A20 directly binds with NEK7, mediating its K48-linked ubiquitination, thereby targeting NEK7 for proteasomal degradation. Our results demonstrate that A20 enhances the ubiquitination of NEK7 at K189 and K293 ubiquitinated sites, with K189 playing a crucial role in the binding of NEK7 to A20, albeit not significantly influencing the interaction between NEK7 and NLRP3. Furthermore, A20 disrupts the association of NEK7 with the NLRP3 complex, potentially through the OTU domain and/or synergistic effect of ZnF4 and ZnF7 motifs. Significantly, NEK7 deletion markedly attenuates the activation of the NLRP3 inflammasome in A20-deficient conditions, both in vitro and in vivo. This study uncovers a mechanism by which A20 inhibits the NLRP3 inflammasome.
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