ArticleCell reports2020
Activation of the CARD8 Inflammasome Requires a Disordered Region.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 53 citations in OpenAlex.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Integrated Cytokine, Metabolic, and Proliferative Profiling Reveals Divergent Metabolic and Proliferative Responses in Papillary Thyroid Cancer Cells.International journal of molecular sciences · 2026Article
- DPP9-mediated inflammasome repression protects against checkpoint inhibitor lung toxicity.bioRxiv : the preprint server for biology · 2026Article
- Evolutionary trajectories, early diversification, and species-specific amplification of the metazoan inhibitor of apoptosis (IAP) repertoire.Molecular biology and evolution · 2026Article
- An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Caspase Recruitment Domain Family Member 8: A Favorable Target in the Pathogenesis of Atherosclerosis.Reviews in cardiovascular medicine · 2026Review
- Inflammasomes and pyroptosis in cancer: mechanisms and therapeutic advances.Journal of hematology & oncology · 2025Review
- Evasion of CARD8 activation during HIV-1 assembly.Science advances · 2025Article
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Viral effectors trigger innate immunity across the tree of life.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Innate immune mechanisms of infection: what we know and potential conserved mechanisms affecting sleep during infection.Neurobiology of sleep and circadian rhythms · 2025Article
- The serine protease DPP9 and the redox sensor KEAP1 form a mutually inhibitory complex.The Journal of biological chemistry · 2025Article
- Protein disorder - function paradigm: Putative role in inflammation.Bioinformation · 2025Article
- Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis.Immunological reviews · 2025Review
- Activation of Inflammasomes and Relevant Modulators for the Treatment of Microglia-mediated Neuroinflammation in Ischemic Stroke.Molecular neurobiology · 2024Review
- 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
- Unanticipated Loss of Inflammasomes in Birds.Genome biology and evolution · 2024Article
- CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity.Cells · 2024Review
- Fusobacterium nucleatum infection modulates the transcriptome and epigenome of HCT116 colorectal cancer cells in an oxygen-dependent manner.Communications biology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Several cytosolic pattern-recognition receptors (PRRs) form multiprotein complexes called canonical inflammasomes in response to intracellular danger signals. Canonical inflammasomes recruit and activate caspase-1 (CASP1), which in turn cleaves and activates inflammatory cytokines and gasdermin D (GSDMD), inducing pyroptotic cell death. Inhibitors of the dipeptidyl peptidases DPP8 and DPP9 (DPP8/9) activate both the human NLRP1 and CARD8 inflammasomes. NLRP1 and CARD8 have different N-terminal regions but have similar C-terminal regions that undergo autoproteolysis to generate two non-covalently associated fragments. Here, we show that DPP8/9 inhibition activates a proteasomal degradation pathway that targets disordered and misfolded proteins for destruction. CARD8's N terminus contains a disordered region of ∼160 amino acids that is recognized and destroyed by this degradation pathway, thereby freeing its C-terminal fragment to activate CASP1 and induce pyroptosis. Thus, CARD8 serves as an alarm to signal the activation of a degradation pathway for disordered and misfolded proteins.
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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.