Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313643997> ?p ?o ?g. }
- W4313643997 abstract "Abstract The non-canonical inflammasome is a signalling complex critical for cell defence against cytosolic Gram-negative bacteria. A key step in the human non-canonical 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, although the molecular mechanisms that activate caspase-4 and govern its capacity to cleave substrates are poorly defined. Caspase-11, the murine counterpart of caspase-4, acquires protease activity within the non-canonical inflammasome by forming a dimer that self-cleaves at D285 to directly cleave GSDMD. These cleavage events trigger signalling via the NLRP3-ASC-caspase-1 axis, leading to downstream cleavage of the pro-interleukin-1β (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 generates 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." @default.
- W4313643997 created "2023-01-07" @default.
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- W4313643997 date "2023-01-06" @default.
- W4313643997 modified "2023-09-30" @default.
- W4313643997 title "Caspase-4 dimerisation and D289 auto-processing elicits an interleukin-1β converting enzyme" @default.
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- W4313643997 doi "https://doi.org/10.1101/2023.01.05.522955" @default.
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