Matches in SemOpenAlex for { <https://semopenalex.org/work/W4312067663> ?p ?o ?g. }
- W4312067663 abstract "Summary Plasma membrane accumulation of phosphorylated mixed lineage kinase domain-like (MLKL) is a hallmark of necroptosis, leading to membrane rupture and inflammatory cell death. Pro-death functions of MLKL are tightly controlled by several checkpoints, including phosphorylation. Endocytosis and exocytosis limit MLKL membrane accumulation and counteract necroptosis, but the exact mechanisms remain poorly understood. Here, we identify linear ubiquitin chain assembly complex (LUBAC)-mediated M1 poly-ubiquitination (poly-Ub) as novel checkpoint for necroptosis regulation downstream of activated MLKL in human cells. Loss of LUBAC activity inhibits necroptosis, without affecting necroptotic signaling, but by preventing membrane accumulation of activated MLKL. Flotillin-1/2 act as putative necroptotic M1 poly-Ub targets that inhibit necroptosis suppression induced by LUBAC inhibition. Finally, we confirm LUBAC-dependent activation of necroptosis in primary human pancreatic organoids. Our findings identify LUBAC as species-specific regulator of necroptosis which promotes MLKL membrane accumulation and pioneer primary human organoids to model necroptosis in near-physiological settings." @default.
- W4312067663 created "2023-01-04" @default.
- W4312067663 creator A5008293391 @default.
- W4312067663 creator A5009680251 @default.
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- W4312067663 creator A5059318668 @default.
- W4312067663 creator A5059867518 @default.
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- W4312067663 creator A5076405967 @default.
- W4312067663 creator A5078834655 @default.
- W4312067663 creator A5088439261 @default.
- W4312067663 date "2022-12-10" @default.
- W4312067663 modified "2023-10-15" @default.
- W4312067663 title "Species-specific LUBAC-mediated M1 ubiquitination regulates necroptosis by segregating the cellular distribution and fate of activated MLKL" @default.
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