Caspase?9 acts as a regulator of necroptotic cell death
نویسندگان
چکیده
Necroptosis is a regulated necrotic-like cell death modality which has come into the focus of attention since it known to contribute pathogenesis many inflammatory and degenerative diseases as well tumor regulation. Based on current data, necroptosis serves backup mechanism when receptor-induced apoptosis inhibited or absent. However, necroptotic role proteins involved in mitochondrial not been investigated. Here, we demonstrated that stimulation several pattern recognition receptors induced under caspase-compromised conditions wild-type, but caspase-9-negative human Jurkat murine MEF cells. Cerulein-induced pancreatitis was significantly reduced mice with acinar cell-restricted caspase-9 gene knockout. The absence led impaired association receptor-interacting serine/threonine-protein kinase 1 (RIPK1) RIPK3 resulted decreased phosphorylation RIP kinases, overexpression RIPK1 rescued effect deficiency. Inhibition either Aurora A (AURKA) its substrate, glycogen synthase 3? (GSK3ß) restored sensitivity caspase-9-deficient cells, indicating an interplay between AURKA-mediated pathways regulate necroptosis. Our findings suggest acts newly identified regulator necroptosis, thus, provides promising therapeutic target manipulate immunological outcome death.
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ژورنال
عنوان ژورنال: FEBS Journal
سال: 2021
ISSN: ['1742-464X', '1742-4658']
DOI: https://doi.org/10.1111/febs.15898