ArticleScience immunology2021
Evolution-inspired redesign of the LPS receptor caspase-4 into an interleukin-1β converting enzyme.
Article in Science immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- When folding CARDs wins the game: molecular snapshots of lipopolysaccharide sensing by the non-canonical inflammasome.Biochemical Society transactions · 2026Review
- Purine and pyrimidine-based bacterial cyclic dinucleotides egress the phagosome and activate the innate immune sensor STING.Immunity · 2026Article
- GBP1 recruitment to actin-rich pedestals of extracellular Gram-negative bacteria promotes pyroptosis.The EMBO journal · 2026Article
- Diffuse alveolar damage, acute respiratory distress syndrome (ARDS), and non-cardiogenic pulmonary edema (NCPE). Part 2: NCPE apart from ARDS, molecular and cellular consequences of primary injury to the lung interstitium, with comparative immunology of the dog and cat.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2026Review
- GBP1 recruitment to actin-rich pedestals induced by extracellular Gram negative bacteria promotes pyroptosis.bioRxiv : the preprint server for biology · 2025Article
- Cardiolipin inhibits the non-canonical inflammasome by preventing LPS binding to caspase-4/11.The EMBO journal · 2025Article
- Evolutionary and functional analyses reveal a role for the RHIM in tuning RIPK3 activity across vertebrates.eLife · 2025Article
- LPS binding caspase activation and recruitment domains (CARDs) are bipartite lipid binding modules.Science advances · 2025Article
- Evolutionary Dynamics of Proinflammatory Caspases in Primates and Rodents.Molecular biology and evolution · 2024Article
- Article
- LPS binding caspase activation and recruitment domains (CARDs) are bipartite lipid binding modules.bioRxiv : the preprint server for biology · 2024Article
- Evolutionary dynamics of pro-inflammatory caspases in primates and rodents.bioRxiv : the preprint server for biology · 2024Article
- Andrographolide Inhibits Expression of NLPR3 Inflammasome in Canine Mononuclear Leukocytes.Animals : an open access journal from MDPI · 2024Article
- Article
- Unanticipated Loss of Inflammasomes in Birds.Genome biology and evolution · 2024Article
- Caspase-5: Structure, Pro-Inflammatory Activity and Evolution.Biomolecules · 2024Review
- The tetrapeptide sequence of IL-18 and IL-1β regulates their recruitment and activation by inflammatory caspases.Cell reports · 2023Article
- Article
- Caspase-4 dimerisation and D289 auto-processing elicit an interleukin-1β-converting enzyme.Life science alliance · 2023Article
- Beyond natural biology: rewiring cellular networks to study innate immunity.Current opinion in immunology · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Innate immune signaling pathways comprise multiple proteins that promote inflammation. This multistep means of information transfer suggests that complexity is a prerequisite for pathway design. Herein, we test this hypothesis by studying caspases that regulate inflammasome-dependent inflammation. Several caspases differ in their ability to recognize bacterial LPS and cleave interleukin-1β (IL-1β). No caspase is known to contain both activities, yet distinct caspases with complementary activities bookend an LPS-induced pathway to IL-1β cleavage. Using caspase-1/4 hybrid proteins present in canines as a guide, we identified molecular determinants of IL-1β cleavage specificity within caspase-1. This knowledge enabled the redesign of human caspase-4 to operate as a one-protein signaling pathway, which intrinsically links LPS detection to IL-1β cleavage and release, independent of inflammasomes. We identified caspase-4 homologues in multiple carnivorans which display the activities of redesigned human caspase-4. These findings illustrate natural signaling pathway diversity and highlight how multistep innate immune pathways can be condensed into a single protein.
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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.