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- Title
Location, location, location: A compartmentalized view of TNF-induced necroptotic signaling.
- Authors
Samson, André L.; Garnish, Sarah E.; Hildebrand, Joanne M.; Murphy, James M.
- Abstract
Necroptosis is a lytic, proinflammatory cell death pathway, which has been implicated in host defense and, when dysregulated, the pathology of many human diseases. The central mediators of this pathway are the receptor-interacting serine/threonine protein kinases RIPK1 and RIPK3 and the terminal executioner, the pseudokinase mixed lineage kinase domain–like (MLKL). Here, we review the chronology of signaling along the RIPK1-RIPK3-MLKL axis and highlight how the subcellular compartmentalization of signaling events controls the initiation and execution of necroptosis. We propose that a network of modulators surrounds the necroptotic signaling core and that this network, rather than acting universally, tunes necroptosis in a context-, cell type–, and species-dependent manner. Such a high degree of mechanistic flexibility is likely an important property that helps necroptosis operate as a robust, emergency form of cell death.
- Subjects
PROTEIN kinases; CELL death; EXECUTIONS &; executioners; SERINE
- Publication
Science Signaling, 2021, Vol 14, Issue 668, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.abc6178