Journal article

Location, location, location: A compartmentalized view of TNF-induced necroptotic signaling

Andre L Samson, Sarah E Garnish, Joanne M Hildebrand, James M Murphy



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 univ..

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Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by IRIISS

Funding Acknowledgements

We acknowledge National Health and Medical Research Council of Australia (NHMRC) grants 2002965 to A.L.S., 1105023 and 1142669 to J.M.H., 1172929 to J.M.M., and IRIISS 9000653; Victorian State Government Operational Infrastructure Support; and CASS Foundation grants to A.L.S. and J.M.H. S.E.G. acknowledges support from an Australian Government Research Training Program Stipend Scholarship and the Wendy Dowsett Scholarship.