Location, location, location: A compartmentalized view of TNF-induced necroptotic signaling
- Author(s)
- Samson, AL; Garnish, SE; Hildebrand, JM; Murphy, JM;
- Details
- Publication Year 2021-02-02,Volume 14,Issue #668,Page eabc6178
- Journal Title
- Science Signaling
- 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.
- Publisher
- AAAS
- Research Division(s)
- Inflammation
- PubMed ID
- 33531383
- Publisher's Version
- https://doi.org/10.1126/scisignal.abc6178
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-03-09 01:37:06
Last Modified: 2022-02-21 02:02:56