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Abstract: Cytoplasmic recognition of microbial lipopolysaccharides (LPS) in human cells is elicited by the caspase-4 and caspase-5 noncanonical inflammasomes, which induce a form of inflammatory cell death termed pyroptosis. Here we show that LPS-mediated activation of caspase-4 also induces a stress response promoting cellular senescence, which is dependent on the caspase-4 substrate gasdermin-D and the tumor suppressor p53. Furthermore, we found that the caspase-4 noncanonical inflammasome is induced and assembled in response to oncogenic RAS signaling during oncogene-induced senescence (OIS). Moreover, targeting caspase-4 expression in OIS showed its critical role in the senescence-associated secretory phenotype and the cell cycle arrest induced in cellular senescence. Finally, we observed that caspase-4 induction occurs in vivo in mouse models of tumor suppression and ageing. Altogether, we are showing that cellular senescence is induced by cytoplasmic LPS recognition by the noncanonical inflammasome and that this pathway is conserved in the cellular response to oncogenic stress.
Fuente: Cell Death and Differentiation, 2022, 29(6), 1267-1282
Publisher: Nature Publishing Group
Year of publication: 2022
No. of pages: 16
Publication type: Article
DOI: 10.1038/s41418-021-00917-6
ISSN: 1476-5403,1350-9047
Publication Url: https://doi.org/10.1038/s41418-021-00917-6
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UCrea Repository Read publication
FERNÁNDEZ-DURAN, IRENE
QUINTANILLA, ANDREA
TARRATS, NÚRIA
BIRCH, JODIE
HARI, PRIYA
MILLAR, FRASER R
LAGNADO, ANTHONY B
SMER-BARRETO, VANESSA
MUIR, MORWENNA
BRUNTON, VALERIE G
PASSOS, JOÃO F
JUAN CARLOS ACOSTA COBACHO
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