ArticleThe EMBO journal2020
PLK4 deubiquitination by Spata2-CYLD suppresses NEK7-mediated NLRP3 inflammasome activation at the centrosome.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- The impact of post-translational modifications and subcellular localization on NLRP3 inflammasome activation: A systematic review.Cell communication and signaling : CCS · 2025Pooled it
- Caspase-3 cleaves CYLD to restrict interferon signaling during mitochondrial apoptosis.EMBO reports · 2026Article
- Linear ubiquitin chain assembly complex contributes to NLRP3-mediated pyroptotic cell death.iScience · 2026Article
- Hydroxytyrosol attenuates obesity-induced myocardial fibrosis by inhibiting NLRP3/CYLD/NOX4 mediated oxidative stress.NPJ science of food · 2026Article
- Human NLRP3 inflammasome activation leads to formation of condensate at the microtubule organizing center.Science advances · 2026Article
- Exploring potential biomarkers of NETosis-Related genes in spinal cord injury through machine learning and multi-omics analysis.Biochemistry and biophysics reports · 2026Article
- Diverse Scaffolds Facilitate NLRP3 Clustering and Inflammasome Formation in Response to Perturbations in Cell Homeostasis.BioEssays : news and reviews in molecular, cellular and developmental biology · 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
- Probing the role of membrane in neutralizing activity of antibodies against influenza virus.Structure (London, England : 1993) · 2026Article
- Organelle stress in NLRP3 inflammasome: a central mediator of neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- NIMA-related kinase family at the nexus of skeletal development and congenital arthrogryposis: coordinated regulation of cell cycle and ciliary dynamics.Frontiers in genetics · 2026Review
- Targeting microglia microtubules: cytoskeletal remodeling as a druggable hub in neuroinflammation and neurodegeneration.Frontiers in neuroscience · 2026Review
- Deciphering the NEK7-NLRP3 inflammasome assembly: from conformational activation to allosteric drug discovery.Frontiers in immunology · 2026Review
- NEKfla: A Genetically Encoded Förster Resonance Energy Transfer Biosensor for Live-Cell Monitoring of Early NIMA-Related Kinase 7-NLR Family Pyrin Domain Containing 3 Inflammasome Signaling.Biomaterials research · 2026Article
- The Gut Microbiota-NLRP3 Inflammasome Axis in Chronic Heart Failure: Mechanisms Across Heart Failure Phenotypes and Therapeutic Perspectives.Journal of inflammation research · 2026Review
- Review
- GSK461364 Inhibits NLRP3 Inflammasome by Targeting NEK7 Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Role of the NLRP3 inflammasome in diabetes and its complications (Review).Molecular medicine reports · 2025Review
- Context-dependent roles of palmitoylation in acute respiratory distress syndrome: integrating inflammation, cell death and repair.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Exploring the role of palmitoylation in sepsis: mechanistic insights and future perspectives.Molecular medicine (Cambridge, Mass.) · 2025Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The innate immune sensor NLRP3 assembles an inflammasome complex with NEK7 and ASC to activate caspase-1 and drive the maturation of proinflammatory cytokines IL-1β and IL-18. NLRP3 inflammasome activity must be tightly controlled, as its over-activation is involved in the pathogenesis of inflammatory diseases. Here, we show that NLRP3 inflammasome activation is suppressed by a centrosomal protein Spata2. Spata2 deficiency enhances NLRP3 inflammasome activity both in the macrophages and in an animal model of peritonitis. Mechanistically, Spata2 recruits the deubiquitinase CYLD to the centrosome for deubiquitination of polo-like kinase 4 (PLK4), the master regulator of centrosome duplication. Deubiquitination of PLK4 facilitates its binding to and phosphorylation of NEK7 at Ser204. NEK7 phosphorylation in turn attenuates NEK7 and NLRP3 interaction, which is required for NLRP3 inflammasome activation. Pharmacological or shRNA-mediated inhibition of PLK4, or mutation of the NEK7 Ser204 phosphorylation site, augments NEK7 interaction with NLRP3 and causes increased NLRP3 inflammasome activation. Our study unravels a novel centrosomal regulatory pathway of inflammasome activation and may provide new therapeutic targets for the treatment of NLRP3-associated inflammatory diseases.
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Registered trials
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.