title: More to life than death: molecular determinants of necroptotic and non-necroptotic RIP3 kinase signaling.
abstract: Necroptosis describes a pro-inflammatory form of cell death governed by the kinases RIP1 and RIP3. Necroptosis can occur following stimulation of the DNA receptor, DAI, or activation of death receptor, Toll-like receptor, T-cell antigen receptor, or interferon receptor signaling. Analysis of RIP3 deficient mice has implicated necroptosis in several inflammatory-driven diseases, including atherosclerosis, alcoholic liver disease and retinal degeneration. Although studies have demonstrated that mixed lineage kinase domain-like (MLKL) is the only substrate of RIP3 kinase that is essential for necroptotic death, the molecular determinants acting downstream of MLKL remain ambiguous. In addition, RIP3 can signal necroptosis independent of RIP1, may induce apoptosis, and can directly promote pro-inflammatory cytokine production. Therefore it will be important to determine if non-necroptotic RIP3 signaling influences RIP3 dependent pathologies.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Nufail
authors.initials: N
authors.lastname: Khan
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Lawlor
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: James M
authors.initials: JM
authors.lastname: Murphy
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3050, Australia. Electronic address: vince@wehi.edu.au.
authors.forename: James E
authors.initials: JE
authors.lastname: Vince
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D053181:Caspase 8 / Q000502:physiology; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D053222:Fas Ligand Protein / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D009336:Necrosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000172:deficiency / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013379:Substrate Specificity / Q000235:genetics / Q000276:immunology
chemical_list: D053222:Fas Ligand Protein; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; C570694:MLKL protein, mouse; D011494:Protein Kinases; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C485615:Ripk3 protein, mouse; D053181:Caspase 8