ArticleCell reports2023
Protein folding stress potentiates NLRP1 and CARD8 inflammasome activation.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.The Journal of clinical investigation · 2026Article
- 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
- Advances in the research of gasdermin-dependent pyroptosis mechanisms and therapeutic targets in inflammatory diseases.Apoptosis : an international journal on programmed cell death · 2026Review
- Caspase Recruitment Domain Family Member 8: A Favorable Target in the Pathogenesis of Atherosclerosis.Reviews in cardiovascular medicine · 2026Review
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- The non-structural protein of SFTSV activates NLRP1 and CARD8 inflammasome through disrupting the DPP9-mediated ternary complex.PLoS pathogens · 2025Article
- Pyroptosis and chemical classification of pyroptotic agents.Molecular diversity · 2025Review
- The serine protease DPP9 and the redox sensor KEAP1 form a mutually inhibitory complex.The Journal of biological chemistry · 2025Article
- Role of inflammasomes and neuroinflammation in epilepsy.Immunological reviews · 2025Review
- Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis.Immunological reviews · 2025Review
- The hydrophobicity of the CARD8 N-terminus tunes inflammasome activation.Cell chemical biology · 2024Article
- A viral E3 ubiquitin ligase produced by herpes simplex virus 1 inhibits the NLRP1 inflammasome.The Journal of experimental medicine · 2024Article
- Mechanistic insights from inflammasome structures.Nature reviews. Immunology · 2024Review
- CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity.Cells · 2024Review
- Inhibition of Leukotriene ACartilage · 2024Article
- Article
- NLRP inflammasomes in health and disease.Molecular biomedicine · 2024Review
- The NLR family of innate immune and cell death sensors.Immunity · 2024Review
- Inflammasome activity regulation by PUFA metabolites.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
NLRP1 and CARD8 are related pattern-recognition receptors (PRRs) that detect intracellular danger signals and form inflammasomes. Both undergo autoproteolysis, generating N-terminal (NT) and C-terminal (CT) fragments. The proteasome-mediated degradation of the NT releases the CT from autoinhibition, but the stimuli that trigger NT degradation have not been fully elucidated. Here, we show that several distinct agents that interfere with protein folding, including aminopeptidase inhibitors, chaperone inhibitors, and inducers of the unfolded protein response, accelerate NT degradation. However, these agents alone do not trigger inflammasome formation because the released CT fragments are physically sequestered by the serine dipeptidase DPP9. We show that DPP9-binding ligands must also be present to disrupt these complexes and allow the CT fragments to oligomerize into inflammasomes. Overall, these results indicate that NLRP1 and CARD8 detect a specific perturbation that induces both protein folding stress and DPP9 ligand accumulation.
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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.