ArticleScience (New York, N.Y.)2019
N-terminal degradation activates the NLRP1B inflammasome.
Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
199 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Insight Into Inflammasome Signaling: Implications forFrontiers in immunology · 2020Pooled it
- The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death.Cellular & molecular immunology · 2026Review
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- Review
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.The Journal of clinical investigation · 2026Article
- IFN-α and IFN-β inhibit NLRP1-driven PANoptosis.EMBO reports · 2026Article
- Molecular insights into NLRP1 Gly/N-degron recognition by CRL2Acta crystallographica. Section F, Structural biology communications · 2026Article
- Cell-autonomous immunity as an integrated immune network against bacterial and viral pathogens.Nature microbiology · 2026Review
- Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer.Cancer science · 2026Review
- DPP9-mediated inflammasome repression protects against checkpoint inhibitor lung toxicity.bioRxiv : the preprint server for biology · 2026Article
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.bioRxiv : the preprint server for biology · 2026Article
- Structure of the E3 ligase CRL2Cell reports · 2026Article
- NLR Inflammasomes in Viral Infections: From Molecular Mechanisms to Therapeutic Interventions.Viruses · 2026Review
- Prevalence, Virulence, and Pathogenic Mechanisms of Mastitis-AssociatedVeterinary sciences · 2026Review
- NLRP1B is an integrated decoy that subvertsProceedings of the National Academy of Sciences of the United States of America · 2026Article
- MST1 promotes microglial pyroptosis and neuroinflammation in alzheimer's disease by regulating the novel DPP8/NLRP1/Caspase-1/GSDMD-N axis.Journal of neuroinflammation · 2026Article
- TAK1 integrates the NLRP1 inflammasome into the innate immune response to double-stranded RNA.bioRxiv : the preprint server for biology · 2026Article
- Intrinsically disordered regions in the NLRP family of receptors act as regulatory hubs for inflammasome condensation and activation.Frontiers in immunology · 2026Article
- Macrophage pyroptosis in inflammatory bowel disease: mechanistic insights, pathological roles and treatment strategies.Frontiers in immunology · 2026Review
- Supramolecular Assemblies Drive Activation of Inflammasomes.Advances in experimental medicine and biology · 2026Review
139 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
Abstract
Intracellular pathogens and danger signals trigger the formation of inflammasomes, which activate inflammatory caspases and induce pyroptosis. The anthrax lethal factor metalloprotease and small-molecule DPP8/9 inhibitors both activate the NLRP1B inflammasome, but the molecular mechanism of NLRP1B activation is unknown. In this study, we used genome-wide CRISPR-Cas9 knockout screens to identify genes required for NLRP1B-mediated pyroptosis. We discovered that lethal factor induces cell death via the N-end rule proteasomal degradation pathway. Lethal factor directly cleaves NLRP1B, inducing the N-end rule-mediated degradation of the NLRP1B N terminus and freeing the NLRP1B C terminus to activate caspase-1. DPP8/9 inhibitors also induce proteasomal degradation of the NLRP1B N terminus but not via the N-end rule pathway. Thus, N-terminal degradation is the common activation mechanism of this innate immune sensor.
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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.