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New insights into Gasdermin D pore formation
Biochemical Society TransactionsGasdermin D (GSDMD) is a pore-forming protein that perforates the plasma membrane (PM) during pyroptosis, a pro-inflammatory form of cell death, to induce the unconventional secretion of inflammatory cytokines and, ultimately, cell lysis. GSDMD is activated by protease-mediated cleavage of its active N-terminal domain from the autoinhibitory C-terminal
Shirin Kappelhoff +2 more
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Protein Expression and Purification, 2021
Gasdermin-D (GSDMD) is a member of the gasdermin (Gsdm) protein family, and its cleavage by inflammatory cysteine proteases (caspases, CASPs) is a critical event in cell pyroptosis. The role and functions of GSDMD on mice and humans are widely studied, but its expression, structure, and function in other species are less known.
Jiameng, Song +4 more
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Gasdermin-D (GSDMD) is a member of the gasdermin (Gsdm) protein family, and its cleavage by inflammatory cysteine proteases (caspases, CASPs) is a critical event in cell pyroptosis. The role and functions of GSDMD on mice and humans are widely studied, but its expression, structure, and function in other species are less known.
Jiameng, Song +4 more
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Biochemical Methods for Assessing Gasdermin D Inactivation in Macrophages
2023Gasdermin D is an essential mediator of pyroptosis. Under resting conditions gasdermin D is inactive in the cytosol. Following inflammasome activation, gasdermin D undergoes processing and oligomerization to create membrane pores and induce pyroptosis to release mature IL-1 and IL-18.
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Progress in small-molecule inhibitors of gasdermin D
European Journal of Medicinal ChemistryAs a key mediator of pyroptosis, Gasdermin D (GSDMD) drives pro-inflammatory cell death through caspase-mediated cleavage to form membrane pores, which is closely linked to the pathogenesis of sepsis, cancer, and autoimmune diseases. Recent advances in GSDMD inhibitor development primarily focus on key steps: blocking caspase-mediated cleavage ...
Yixuan Shua +3 more
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D-aring to explore: New approaches to gasdermin D targeting
Cell Chemical BiologyNovel inhibitors of pyroptosis promise breakthroughs in treating inflammatory diseases and malignant tumors. In this issue of Cell Chemical Biology, Hu et al.1 identify two repurposed drugs that selectively target gasdermin D (GSDMD) oligomers, effectively suppressing pyroptosis while reducing off-target effects typical of cysteine-based inhibitors.
Lei, Wang, Wen, Zhou
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Gasdermin D palmitoylation: to cleave or not to cleave?
Trends in ImmunologyRecent studies have identified Cys191 in gasdermin D (GSDMD) as a highly targeted regulatory module controlling pyroptosis. Using chemical biology and genetic models, Du, Healy et al. recently identified GSDMD palmitoylation as a key regulatory step in GSDMD activation.
Laurel Stine, Fiachra Humphries
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IRF2 induces gasdermin D for pyroptosis
Science, 2019Immunology Inflammasome activation triggers the cleavage of the protein gasdermin D. The N-terminal fragments oligomerize and form pores in the plasma membrane, leading to the release of the inflammatory cytokine interleukin-1β (IL-1β) and cell death by pyroptosis. Kayagaki et al.
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Gasdermin D-Mediated Pyroptosis Promotes the Development of Atherosclerosis
Laboratory InvestigationAtherosclerosis is a chronic inflammatory cardiovascular disease with a high-morbidity and mortality rate. An increasing number of studies have addressed the crucial contribution of gasdermin D (GSDMD)-mediated pyroptosis, which is triggered by the inflammasomes to the development of atherosclerosis.
Bangbang Huang +6 more
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Gut instincts: Gasdermin D feeds while it fights
ImmunityThe small intestine coordinates nutrient absorption and immune defense, but the epithelial signaling mechanisms bridging these functions are unclear. In this issue of Immunity, Yu et al. reveal a gasdermin-D-driven circuit that links lipid uptake and enterocyte metabolism to γδ T cell maintenance and barrier protection.
Paola Brescia, Maria Rescigno
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Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway
Cell, 2021Iva Hafner Bratković +2 more
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