ArticleeLife2024
Caspase-1 activates gasdermin A in non-mammals.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Pyroptosis in Peripheral Neuropathy: From Molecular Mechanisms to Therapeutic Targeting.CNS neuroscience & therapeutics · 2026Pooled it
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Igniting antitumour immunity with cancer cell pyroptosis.Nature reviews. Cancer · 2026Review
- Coronavirus Nsp5‑mediated dual‑site cleavage of GSDMA modifies its antiviral and proinflammatory functions.PLoS pathogens · 2026Article
- Theme and variations: activation and regulation of gasdermin-mediated inflammation.Biochemical Society transactions · 2026Review
- Novel duck reovirus σC hijacks the mitochondrial COQ6-CoQ10 axis to drive NLRP3-dependent pyroptosis.PLoS pathogens · 2026Article
- Pyroptosis: Turning Up the Heat on Cancer.Annual review of immunology · 2026Review
- Gasdermins against intracellular bacterial pathogens.Nature microbiology · 2026Review
- Gasdermins in neurodegeneration: emerging mechanisms and therapeutic targets.Cell death & disease · 2025Review
- Staphylococcus aureus induces Gasdermin A-dependent keratinocyte pyroptosis.Nature communications · 2025Article
- GSDMD and GSDME exhibit distinct roles in enteric coronavirus PDCoV-induced pyroptosis and inflammatory responses.Journal of virology · 2025Article
- Mechanistic insights into gasdermin-mediated pyroptosis.Nature reviews. Molecular cell biology · 2025Review
- Pyroptosis: molecular mechanisms and roles in disease.Cell research · 2025Review
- The EMCV protein 2B* is required for efficient cell lysis via both caspase-3-dependent and -independent pathways during infection.The Journal of general virology · 2025Article
- Dialogue between programmed cell death and psoriasis.Postepy dermatologii i alergologii · 2025Review
- Targeting programmed cell death with natural products: a potential therapeutic strategy for diminished ovarian reserve and fertility preservation.Frontiers in pharmacology · 2025Review
- Administration of 2-deoxy-D-glucose induces pyroptosis in murine breast cancer cells via cAMP/PKA/HK2 to impair tumor survival.Frontiers in immunology · 2025Article
- Pyroptosis: Induction and inhibition strategies for immunotherapy of diseases.Acta pharmaceutica Sinica. B · 2024Review
- Gasdermins as evolutionarily conserved executors of inflammation and cell death.Nature cell biology · 2024Review
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family. A gene duplication of GSDMA in the common ancestor of caecilian amphibians, reptiles, and birds gave rise to GSDMA-D in mammals. Uniquely in our tree, amphibian, reptile, and bird GSDMA group in a separate clade than mammal GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals.
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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.