title: Necroptosis-independent signaling by the RIP kinases in inflammation.
abstract: Recent advances have identified a signaling cascade involving receptor interacting protein kinase 1 (RIPK1), RIPK3 and the pseudokinase mixed lineage kinase domain-like (MLKL) that is crucial for induction of necroptosis, a non-apoptotic form of cell death. RIPK1-RIPK3-MLKL-mediated necroptosis has been attributed to cause many inflammatory diseases through the release of cellular damage-associated molecular patterns (DAMPs). In addition to necroptosis, emerging evidence suggests that these necroptosis signal adaptors can also facilitate inflammation independent of cell death. In particular, the RIP kinases can drive NF-κB and inflammasome activation independent of cell death. In this review, we will discuss recent discoveries that led to this realization and present arguments why cell death-independent signaling by the RIP kinases may have a more important role in inflammation than necroptosis.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
authors.forename: Kenta
authors.initials: K
authors.lastname: Moriwaki
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA. francis.chan@umassmed.edu.
authors.forename: Francis Ka-Ming
authors.initials: FK
authors.lastname: Chan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis / Q000473:pathology*; D011494:Protein Kinases / Q000378:metabolism*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D058847:Inflammasomes; D016328:NF-kappa B; C570694:MLKL protein, mouse; D011494:Protein Kinases; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse; C485615:Ripk3 protein, mouse
keywords: IL-1β; NF-κB; RIPK1; RIPK3; RelB