title: Programmed necrosis in inflammation: Toward identification of the effector molecules.
abstract: Until recently, programmed cell death was conceived of as a single set of molecular pathways. We now know of several distinct sets of death-inducing mechanisms that lead to differing cell-death processes. In one of them--apoptosis--the dying cell affects others minimally. In contrast, programmed necrotic cell death causes release of immunostimulatory intracellular components after cell-membrane rupture. Defining the in vivo relevance of necrotic death is hampered because the molecules initiating it [such as receptor-interacting protein kinase-1 (RIPK1), RIPK3, or caspase-1] also serve other functions. Proteins that participate in late events in two forms of programmed necrosis [mixed lineage kinase domain-like protein (MLKL) in necroptosis and gasdermin-D in pyroptosis] were recently discovered, bringing us closer to identifying molecules that strictly serve in death mediation, thereby providing probes for better assessing its role in inflammation.
authors.affiliation: Department of Biomolecular Sciences, The Weizmann Institute of Science, 76100 Rehovot, Israel. d.wallach@weizmann.ac.il douglas.green@stjude.org.
authors.forename: David
authors.initials: D
authors.lastname: Wallach
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chung-Ju 380-701, Korea.
authors.forename: Tae-Bong
authors.initials: TB
authors.lastname: Kang
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Dillon
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. d.wallach@weizmann.ac.il douglas.green@stjude.org.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
mesh_terms: D000818:Animals; D017209:Apoptosis; D020170:Caspase 1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins; D009336:Necrosis / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D028044:Phosphate-Binding Proteins; D011494:Protein Kinases / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D000094524:Gasdermins
chemical_list: D020170:Caspase 1; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D028044:Phosphate-Binding Proteins; D011494:Protein Kinases; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C498366:GSDMD protein, human; D000094524:Gasdermins; C570693:MLKL protein, human