ArticleLife science alliance2023
Caspase-4 dimerisation and D289 auto-processing elicit an interleukin-1β-converting enzyme.
Article in Life science alliance, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 28 citations in OpenAlex.
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- When folding CARDs wins the game: molecular snapshots of lipopolysaccharide sensing by the non-canonical inflammasome.Biochemical Society transactions · 2026Review
- An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- New insights into the noncanonical inflammasome point to caspase-4 as a druggable target.Nature reviews. Immunology · 2025Review
- Cardiolipin inhibits the non-canonical inflammasome by preventing LPS binding to caspase-4/11.The EMBO journal · 2025Article
- Gasdermin-D pores induce an inactivating caspase-4 cleavage that limits IL-18 production in the intestinal epithelium.Communications biology · 2025Article
- Pyroptosis: A spoiler of peaceful coexistence between cells in degenerative bone and joint diseases.Journal of advanced research · 2025Review
- Inflammasome-mediated pyroptosis in defense against pathogenic bacteria.Immunological reviews · 2025Review
- Inflammasome components as new therapeutic targets in inflammatory disease.Nature reviews. Immunology · 2025Review
- Cell death in acute lung injury: caspase-regulated apoptosis, pyroptosis, necroptosis, and PANoptosis.Frontiers in pharmacology · 2025Review
- Pyroptotic cell corpses are crowned with F-actin-rich filopodia that engage CLEC9A signaling in incoming dendritic cells.Nature immunology · 2025Article
- Article
- Mechanistic insights from inflammasome structures.Nature reviews. Immunology · 2024Review
- Roles of the Caspase-11 Non-Canonical Inflammasome in Rheumatic Diseases.International journal of molecular sciences · 2024Review
- NLRP3 inflammasome and pyroptosis in cardiovascular diseases and exercise intervention.Frontiers in pharmacology · 2024Review
- The tetrapeptide sequence of IL-18 and IL-1β regulates their recruitment and activation by inflammatory caspases.Cell reports · 2023Article
- Regulated cell death in neutrophils: From apoptosis to NETosis and pyroptosis.Seminars in immunology · 2023Review
- The tetrapeptide sequence of IL-1β regulates its recruitment and activation by inflammatory caspases.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 4 countries.
Funding
Abstract
The noncanonical inflammasome is a signalling complex critical for cell defence against cytosolic Gram-negative bacteria. A key step in the human noncanonical inflammasome pathway involves unleashing the proteolytic activity of caspase-4 within this complex. Caspase-4 induces inflammatory responses by cleaving gasdermin-D (GSDMD) to initiate pyroptosis; however, the molecular mechanisms that activate caspase-4 and govern its capacity to cleave substrates remain poorly defined. Caspase-11, the murine counterpart of caspase-4, acquires protease activity within the noncanonical inflammasome by forming a dimer that self-cleaves at D285 to cleave GSDMD. These cleavage events trigger signalling via the NLRP3-ASC-caspase-1 axis, leading to downstream cleavage of the pro-IL-1β cytokine precursor. Here, we show that caspase-4 first dimerises then self-cleaves at two sites-D270 and D289-in the interdomain linker to acquire full proteolytic activity, cleave GSDMD, and induce cell death. Surprisingly, caspase-4 dimerisation and self-cleavage at D289 generate a caspase-4 p34/p9 protease species that directly cleaves pro-IL-1β, resulting in its maturation and secretion independently of the NLRP3 inflammasome in primary human myeloid and epithelial cells. Our study thus elucidates the key molecular events that underpin signalling by the caspase-4 inflammasome and identifies IL-1β as a natural substrate of caspase-4.
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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.