Necroptosis and Inflammation

Annual Review of Biochemistry

Volumn 85, Issue , 2016, Pages 743-763

  Newton, Kim ^a   Manning, Gerard ^a  

^a GENENTECH INC   (United States)

Author keywords

MLKL; RIPK1; RIPK3

Indexed keywords

CASPASE 8; CASPASE INHIBITOR; MIXED LINEAGE KINASE LIKE PROTEIN; PROCASPASE 8; PROTEIN SERINE THREONINE KINASE; RECEPTOR INTERACTING PROTEIN SERINE THREONINE KINASE 1; RECEPTOR INTERACTING PROTEIN SERINE THREONINE KINASE 3; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); SUCCINATE DEHYDROGENASE (UBIQUINONE); T LYMPHOCYTE RECEPTOR; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR AGONIST; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNCLASSIFIED DRUG; CASP8 PROTEIN, HUMAN; MLKL PROTEIN, HUMAN; PROTEIN KINASE; RECEPTOR INTERACTING PROTEIN SERINE THREONINE KINASE; RIPK1 PROTEIN, HUMAN; RIPK3 PROTEIN, HUMAN; TLR3 PROTEIN, HUMAN;

APOPTOSIS; ARTICLE; AUTOPHOSPHORYLATION; BACTERIAL CLEARANCE; CELL DEATH; ENDOTHELIUM CELL; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; FIBROBLAST; HUMAN; INFLAMMATION; INNATE IMMUNITY; MACROPHAGE; NECROPTOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN PROCESSING; UBIQUITINATION; ANIMAL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; NECROSIS; PATHOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; APOPTOSIS; CASPASE 8; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HUMANS; IMMUNITY, INNATE; INFLAMMATION; NECROSIS; PROTEIN KINASES; RECEPTOR-INTERACTING PROTEIN SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 3; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84974727387     PISSN: 00664154     EISSN: 15454509     Source Type: Book Series    
DOI: 10.1146/annurev-biochem-060815-014830     Document Type: Article

References (147)

1. Kerr JF, Wyllie AH, Currie AR. 1972. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26:239-57
2. Crawford ED, Wells JA. 2011. Caspase substrates and cellular remodeling. Annu. Rev. Biochem. 80:1055-87
3. Ravichandran KS. 2011. Beginnings of a good apoptotic meal: The find-me and eat-me signaling pathways. Immunity 35:445-55
4. Rickard JA, Anderton H, EtemadiN, Nachbur U, DardingM, et al. 2014. TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice. ELife 3:e03464
5. Kumari S, Redouane Y, Lopez-Mosqueda J, Shiraishi R, Romanowska M, et al. 2014. Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis. ELife 3:e03422
6. Panayotova-Dimitrova D, Feoktistova M, Ploesser M, Kellert B, Hupe M, et al. 2013. cFLIP regulates skin homeostasis and protects against TNF-induced keratinocyte apoptosis. Cell Rep. 5:397-408
7. Lamkanfi M, Dixit VM. 2014. Mechanisms and functions of inflammasomes. Cell 157:1013-22
8. Vercammen D, Beyaert R, Denecker G, Goossens V, van Loo G, et al. 1998. Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor. J. Exp. Med. 187:1477-85
9. Vercammen D, Brouckaert G, Denecker G, Van de CraenM, DeclercqW, et al. 1998. Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways. J. Exp. Med. 188:919-30
10. Holler N, Zaru R, Micheau O, Thome M, Attinger A, et al. 2000. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat. Immunol. 1:489-95
11. MatsumuraH, Shimizu Y, Ohsawa Y, Kawahara A, Uchiyama Y, Nagata S. 2000. Necrotic death pathway in Fas receptor signaling. J. Cell. Biol. 151:1247-56
12. Chan FK, Shisler J, Bixby JG, Felices M, Zheng L, et al. 2003. A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. J. Biol. Chem. 278:51613-21
13. Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, et al. 2005. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat. Chem. Biol. 1:112-19
14. Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, et al. 2008. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat. Chem. Biol. 4:313-21
15. Smith CC, Davidson SM, Lim SY, Simpkin JC, Hothersall JS, Yellon DM. 2007. Necrostatin: A potentially novel cardioprotective agent? Cardiovasc. Drugs Ther. 21:227-33
16. Takahashi N, Duprez L, Grootjans S, Cauwels A, Nerinckx W, et al. 2012. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis. 3:e437
17. Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, et al. 2009. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325:332-36
18. Cho YS, Challa S, Moquin D, Genga R, Ray TD, et al. 2009. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137:1112-23
19. He S, Wang L, Miao L, Wang T, Du F, et al. 2009. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-?. Cell 137:1100-11
20. Newton K, Sun X, Dixit VM. 2004. Kinase RIP3 is dispensable for normal NF-?Bs, signaling by the B-cell and T-cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4. Mol. Cell. Biol. 24:1464-69
21. Duprez L, TakahashiN, Van Hauwermeiren F, Vandendriessche B, Goossens V, et al. 2011. RIP kinasedependent necrosis drives lethal systemic inflammatory response syndrome. Immunity 35:908-18
22. Newton K, Dugger DL, Wickliffe KE, Kapoor N, de AlmagroMC, et al. 2014. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science 343:1357-60
23. Lin J, Li H, Yang M, Ren J, Huang Z, et al. 2013. A role of RIP3-mediated macrophage necrosis in atherosclerosis development. Cell Rep. 3:200-10
24. Murakami Y, Matsumoto H, Roh M, Suzuki J, Hisatomi T, et al. 2012. Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration. PNAS 109:14598-603
25. Murakami Y, Matsumoto H, Roh M, Giani A, Kataoka K, et al. 2014. Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsRNA-induced retinal degeneration. Cell Death Differ. 21:270-77
26. Luedde M, Lutz M, Carter N, Sosna J, Jacoby C, et al. 2014. RIP3, a kinase promoting necroptotic cell death, mediates adverse remodelling after myocardial infarction. Cardiovasc. Res. 103:206-16
27. Linkermann A, Brasen JH, Darding M, Jin MK, Sanz AB, et al. 2013. Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. PNAS 110:12024-29
28. Gautheron J, Vucur M, Reisinger F, Cardenas DV, Roderburg C, et al. 2014. A positive feedback loop between RIP3 and JNK controls non-alcoholic steatohepatitis. EMBO Mol. Med. 6:1062-74
29. Vitner EB, Salomon R, Farfel-Becker T, Meshcheriakova A, Ali M, et al. 2014. RIPK3 as a potential therapeutic target for Gaucher's disease. Nat. Med. 20:204-8
30. Roychowdhury S, McMullen MR, Pisano SG, Liu X, Nagy LE. 2013. Absence of receptor interacting protein kinase 3 prevents ethanol-induced liver injury. Hepatology 57:1773-83
31. Micheau O, Tschopp J. 2003. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114:181-90
32. Ermolaeva MA, MichalletMC, Papadopoulou N, Utermohlen O, Kranidioti K, et al. 2008. Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses. Nat. Immunol. 9:1037-46
33. Pobezinskaya YL, Kim YS, Choksi S, MorganMJ, Li T, et al. 2008. The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent Toll-like receptors. Nat. Immunol. 9:1047-54
34. Hsu H, Shu HB, Pan MG, Goeddel DV. 1996. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84:299-308
35. Shu HB, Takeuchi M, Goeddel DV. 1996. The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. PNAS 93:13973-78
36. Vince JE, Pantaki D, Feltham R, Mace PD, Cordier SM, et al. 2009. TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (TNF) to efficiently activate NF-?B and to prevent TNF-induced apoptosis. J. Biol. Chem. 284:35906-15
37. Varfolomeev E, Goncharov T, Fedorova AV, Dynek JN, Zobel K, et al. 2008. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor ? (TNF?)-induced NF-?B activation. J. Biol. Chem. 283:24295-99
38. Mahoney DJ, Cheung HH, Mrad RL, Plenchette S, Simard C, et al. 2008. Both cIAP1 and cIAP2 regulate TNF mediated NF-?B activation. PNAS 105:11778-83
39. Haas TL, Emmerich CH, Gerlach B, Schmukle AC, Cordier SM, et al. 2009. Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNFmediated gene induction. Mol. Cell 36:831-44
40. Cheung PC, Nebreda AR, Cohen P. 2004. TAB3, a new binding partner of the protein kinase TAK1. Biochem. J. 378:27-34
41. Kanayama A, Seth RB, Sun L, Ea CK, Hong M, et al. 2004. TAB2 and TAB3 activate the NF-?B pathway through binding to polyubiquitin chains. Mol. Cell 15:535-48
42. Tokunaga F, Nakagawa T, Nakahara M, Saeki Y, Taniguchi M, et al. 2011. SHARPIN is a component of the NF-?B-activating linear ubiquitin chain assembly complex. Nature 471:633-36
43. Ikeda F, Deribe YL, Skanland SS, Stieglitz B, Grabbe C, et al. 2011. SHARPIN forms a linear ubiquitin ligase complex regulating NF-?B activity and apoptosis. Nature 471:637-41
44. Gerlach B, Cordier SM, Schmukle AC, Emmerich CH, Rieser E, et al. 2011. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature 471:591-96
45. Kirisako T, Kamei K, Murata S, KatoM, FukumotoH, et al. 2006. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J. 25:4877-87
46. Dynek JN, GoncharovT, DueberEC, Fedorova AV, Izrael-Tomasevic A, et al. 2010. c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J. 29:4198-209
47. Rahighi S, Ikeda F, KawasakiM, AkutsuM, SuzukiN, et al. 2009. Specific recognition of linear ubiquitin chains by NEMO is important for NF-?B activation. Cell 136:1098-109
48. Lo YC, Lin SC, Rospigliosi CC, Conze DB, Wu CJ, et al. 2009. Structural basis for recognition of diubiquitins by NEMO. Mol. Cell 33:602-15
49. Emmerich CH, Ordureau A, Strickson S, Arthur JS, Pedrioli PG, et al. 2013. Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains. PNAS 110:15247-52
50. Zhang J, Clark K, Lawrence T, Peggie MW, Cohen P. 2014. An unexpected twist to the activation of IKK?: TAK1 primes IKK?for activation by autophosphorylation. Biochem. J. 461:531-37
51. Newton K, Dixit VM. 2012. Signaling in innate immunity and inflammation. Cold Spring Harb. Perspect. Biol. 4:a006049
52. Dickens LS, Boyd RS, Jukes-Jones R, Hughes MA, Robinson GL, et al. 2012. A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death. Mol. Cell 47:291-305
53. Schleich K, Warnken U, Fricker N, Ozturk S, Richter P, et al. 2012. Stoichiometry of the CD95 deathinducing signaling complex: experimental and modeling evidence for a death effector domain chain model. Mol. Cell 47:306-19
54. Majkut J, Sgobba M, Holohan C, Crawford N, Logan AE, et al. 2014. Differential affinity of FLIP and procaspase 8 for FADD's DED binding surfaces regulates DISC assembly. Nat. Commun. 5:3350
55. Sun L, Wang H, Wang Z, He S, Chen S, et al. 2012. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinasE. Cell 148:213-27
56. Zhao J, Jitkaew S, Cai Z, Choksi S, Li Q, et al. 2012. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. PNAS 109:5322-27
57. Murphy JM, Czabotar PE, Hildebrand JM, Lucet IS, Zhang JG, et al. 2013. The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 39:443-53
58. Wu J, Huang Z, Ren J, Zhang Z, He P, et al. 2013. Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis. Cell Res. 23:994-1006
59. Sun X, Yin J, Starovasnik MA, Fairbrother WJ, Dixit VM. 2002. Identification of a novel homotypic interactionmotif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3. J. Biol. Chem. 277:9505-11
60. Wu XN, Yang ZH, Wang XK, Zhang Y, Wan H, et al. 2014. Distinct roles of RIP1-RIP3 hetero-and RIP3-RIP3 homo-interaction in mediating necroptosis. Cell Death Differ. 21:1709-20
61. Chen W, Zhou Z, Li L, Zhong CQ, Zheng X, et al. 2013. Diverse sequence determinants control human and mouse receptor interacting protein 3 (RIP3) and mixed lineage kinase domain-like (MLKL) interaction in necroptotic signaling. J. Biol. Chem. 288:16247-61
62. Wang H, Sun L, Su L, Rizo J, Liu L, et al. 2014. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol. Cell 54:133-46
63. Su L, Quade B, Wang H, Sun L, Wang X, Rizo J. 2014. A plug release mechanism for membrane permeation by MLKL. Structure 22:1489-500
64. Cai Z, Jitkaew S, Zhao J, ChiangHC, Choksi S, et al. 2014. Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat. Cell Biol. 16:55-65
65. Dondelinger Y, DeclercqW, Montessuit S, Roelandt R, Goncalves A, et al. 2014. MLKL compromises plasma membrane integrity by binding to phosphatidylinositol phosphates. Cell Rep. 7:971-81
66. Hildebrand JM, Tanzer MC, Lucet IS, Young SN, Spall SK, et al. 2014. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. PNAS 111:15072-77
67. Chen X, Li W, Ren J, Huang D, He WT, et al. 2014. Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res. 24:105-21
68. He S, Liang Y, Shao F, Wang X. 2011. Toll-like receptors activate programmed necrosis inmacrophages through a receptor-interacting kinase-3-mediated pathway. PNAS 108:20054-59
69. Kaiser WJ, Sridharan H, Huang C, Mandal P, Upton JW, et al. 2013. Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL. J. Biol. Chem. 288:31268-79
70. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, et al. 2004. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-?B activation. Nat. Immunol. 5:503-7
71. Kaiser WJ, Offermann MK. 2005. Apoptosis induced by the Toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif. J. Immunol. 174:4942-52
72. Polykratis A, Hermance N, Zelic M, Roderick J, Kim C, et al. 2014. Cutting edge: RIPK1 kinase inactive mice are viable and protected from TNF-induced necroptosis in vivo. J. Immunol. 193:1539-43
73. Berger SB, Kasparcova V, Hoffman S, Swift B, Dare L, et al. 2014. Cutting edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice. J. Immunol. 192:5476-80
74. Upton JW, Kaiser WJ, Mocarski ES. 2012. DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virusinduced programmed necrosis that is targeted bymurine cytomegalovirus vIRA. CellHostMicrobe 11:290-97
75. Upton JW, Kaiser WJ, Mocarski ES. 2010. Virus inhibition of RIP3-dependent necrosis. Cell Host Microbe 7:302-13
76. GuoH, Omoto S, Harris PA, Finger JN, Bertin J, et al. 2015. Herpes simplex virus suppresses necroptosis in human cells. Cell Host Microbe 17:243-51
77. Newton K, Harris AW, Bath ML, Smith KG, Strasser A. 1998. A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. EMBO. J. 17:706-18
78. Salmena L, Lemmers B, Hakem A, Matysiak-Zablocki E, Murakami K, et al. 2003. Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. Genes Dev. 17:883-95
79. Zhang H, Zhou X, McQuade T, Li J, Chan FK, Zhang J. 2011. Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature 471:373-76
80. Oberst A, Dillon CP, Weinlich R, McCormick LL, Fitzgerald P, et al. 2011. Catalytic activity of the caspase-8-FLIPL complex inhibits RIPK3-dependent necrosis. Nature 471:363-67
81. Kaiser WJ, Upton JW, Long AB, Livingston-Rosanoff D, Daley-Bauer LP, et al. 2011. RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature 471:368-72
82. Ch'en IL, Tsau JS, Molkentin JD, Komatsu M, Hedrick SM. 2011. Mechanisms of necroptosis in T cells. J. Exp. Med. 208:633-41
83. Lu JV, Weist BM, van Raam BJ, Marro BS, Nguyen LV, et al. 2011. Complementary roles of Fasassociated death domain (FADD) and receptor interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral immunity. PNAS 108:15312-17
84. Leverrier S, Salvesen GS, Walsh CM. 2011. Enzymatically active single chain caspase-8 maintainsT-cell survival during clonal expansion. Cell Death Differ. 18:90-98
85. Welz PS, Wullaert A, Vlantis K, Kondylis V, Fernandez-Majada V, et al. 2011. FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature 477:330-34
86. BonnetMC, Preukschat D, Welz PS, van LooG, Ermolaeva MA, et al. 2011. The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation. Immunity 35:572-82
87. Dillon CP, Oberst A, Weinlich R, Janke LJ, Kang TB, et al. 2012. Survival function of the FADDCASPASE-8-cFLIPL complex. Cell Rep. 1:401-7
88. Weinlich R, Oberst A, Dillon CP, Janke LJ, Milasta S, et al. 2013. Protective roles for caspase-8 and cFLIP in adult homeostasis. Cell Rep. 5:340-48
89. Dillon CP, Weinlich R, Rodriguez DA, Cripps JG, QuaratoG, et al. 2014. RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3. Cell 157:1189-202
90. Kang TB, Oh GS, Scandella E, Bolinger B, Ludewig B, et al. 2008. Mutation of a self-processing site in caspase-8 compromises its apoptotic but not its nonapoptotic functions in bacterial artificial chromosome-transgenic mice. J. Immunol. 181:2522-32
91. Smith KG, Strasser A, Vaux DL. 1996. CrmA expression in T lymphocytes of transgenic mice inhibits CD95 (Fas/APO-1)-transduced apoptosis, but does not cause lymphadenopathy or autoimmune disease. EMBO J. 15:5167-76
92. Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS, et al. 1998. Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity 9:267-76
93. Yeh WC, de la Pompa JL, McCurrach ME, Shu HB, Elia AJ, et al. 1998. FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science 279:1954-58
94. YehWC, Itie A, Elia AJ, Ng M, Shu HB, et al. 2000. Requirement for casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development. Immunity 12:633-42
95. Pop C, Oberst A, Drag M, Van Raam BJ, Riedl SJ, et al. 2011. FLIPL induces caspase 8 activity in the absence of interdomain caspase 8 cleavage and alters substrate specificity. Biochem. J. 433:447-57
96. O'Donnell MA, Perez-Jimenez E, Oberst A, Ng A, Massoumi R, et al. 2011. Caspase 8 inhibits programmed necrosis by processing CYLD. Nat. Cell Biol. 13:1437-42
97. Wright A, Reiley WW, Chang M, Jin W, Lee AJ, et al. 2007. Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD. Dev. Cell 13:705-16
98. Hitomi J, Christofferson DE, Ng A, Yao J, Degterev A, et al. 2008. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell 135:1311-23
99. Wang L, Du F, Wang X. 2008. TNF-?induces two distinct caspase-8 activation pathways. Cell 133:693-703
100. Moquin DM, McQuade T, Chan FK. 2013. CYLD deubiquitinates RIP1 in the TNF induced necrosome to facilitate kinase activation and programmed necrosis. PLOS ONE 8:e76841
101. Kaiser WJ, Daley-BauerLP, ThapaRJ, Mandal P, Berger SB, et al. 2014. RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition. PNAS 111:7753-58
102. McQuade T, Cho Y, Chan FK. 2013. Positive and negative phosphorylation regulates RIP1-and RIP3-induced programmed necrosis. Biochem. J. 456:409-15
103. Weng D, Marty-Roix R, Ganesan S, Proulx MK, Vladimer GI, et al. 2014. Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death. PNAS 111:7391-96
104. Philip NH, Dillon CP, Snyder AG, Fitzgerald P, Wynosky-Dolfi MA, et al. 2014. Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-?B andMAPK signaling. PNAS 111:7385-90
105. Dondelinger Y, Aguileta MA, Goossens V, Dubuisson C, Grootjans S, et al. 2013. RIPK3 contributes to TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion or TAK1 kinase inhibition. Cell Death Differ. 20:1381-92
106. Lamothe B, Lai Y, Xie M, Schneider MD, Darnay BG. 2013. TAK1 is essential for osteoclast differentiation and is an important modulator of cell death by apoptosis and necroptosis. Mol. Cell. Biol. 33:582-95
107. Vanlangenakker N, Vanden Berghe T, Bogaert P, Laukens B, Zobel K, et al. 2011. cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell Death Differ. 18:656-65
108. Moulin M, Anderton H, Voss AK, Thomas T, Wong WW, et al. 2012. IAPs limit activation of RIP kinases by TNF receptor 1 during development. EMBO J. 31:1679-91
109. O'Donnell MA, Hase H, Legarda D, Ting AT. 2012. NEMO inhibits programmed necrosis in an NF?B-independent manner by restraining RIP1. PLOS ONE 7:e41238
110. Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, et al. 1997. Inhibition of death receptor signals by cellular FLIP. Nature 388:190-95
111. Opipari AWJr, Hu HM, Yabkowitz R, Dixit VM. 1992. The A20 zinc finger protein protects cells from tumor necrosis factor cytotoxicity. J. Biol. Chem. 267:12424-27
112. Legarda-Addison D, Hase H, O'Donnell MA, Ting AT. 2009. NEMO/IKK? regulates an early NF-?B-independent cell-death checkpoint during TNF signaling. Cell Death Differ. 16:1279-88
113. de Almagro MC, Goncharov T, Newton K, Vucic D. 2015. Cellular IAP proteins and LUBAC differentially regulate necrosome-associated RIP1 ubiquitination. Cell Death Dis. 6:e1800
114. Kelliher MA, Grimm S, Ishida Y, Kuo F, Stanger BZ, Leder P. 1998. The death domain kinase RIP mediates the TNF-induced NF-?B signal. Immunity 8:297-303
115. Rickard JA, O'Donnell JA, Evans JM, Lalaoui N, Poh AR, et al. 2014. RIPK1 regulates RIPK3-MLKLdriven systemic inflammation and emergency hematopoiesis. Cell 157:1175-88
116. Dannappel M, Vlantis K, Kumari S, Polykratis A, Kim C, et al. 2014. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 513:90-94
117. Takahashi N, Vereecke L, Bertrand MJ, Duprez L, Berger SB, et al. 2014. RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis. Nature 513:95-99
118. Orozco S, Yatim N, Werner MR, Tran H, Gunja SY, et al. 2014. RIPK1 both positively and negatively regulates RIPK3 oligomerization and necroptosis. Cell Death Differ. 21:1511-21
119. FeoktistovaM, Geserick P, Kellert B, Dimitrova DP, Langlais C, et al. 2011. cIAPs block Ripoptosome formation, aRIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol. Cell 43:449-63
120. Tenev T, Bianchi K, Darding M, Broemer M, Langlais C, et al. 2011. The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol. Cell 43:432-48
121. Chen W, Wu J, Li L, Zhang Z, Ren J, et al. 2015. Ppm1b negatively regulates necroptosis through dephosphorylating Rip3. Nat. Cell Biol. 17:434-44
122. Cusson N, Oikemus S, Kilpatrick ED, Cunningham L, Kelliher M. 2002. The death domain kinase RIP protects thymocytes from tumor necrosis factor receptor type 2-induced cell death. J. Exp. Med. 196:15-26
123. Thapa RJ, Nogusa S, Chen P, Maki JL, Lerro A, et al. 2013. Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases. PNAS 110:E3109-18
124. McComb S, Cessford E, Alturki NA, Joseph J, Shutinoski B, et al. 2014. Type-I interferon signaling through ISGF3 complex is required for sustained Rip3 activation and necroptosis in macrophages. PNAS 111:E3206-13
125. Kearney CJ, Cullen SP, Clancy D, Martin SJ. 2014. RIPK1 can function as an inhibitor rather than an initiator of RIPK3-dependent necroptosis. FEBS J. 281:4921-34
126. Gentle IE, Wong WW, Evans JM, Bankovacki A, Cook WD, et al. 2011. In TNF-stimulated cells, RIPK1 promotes cell survival by stabilizing TRAF2 and cIAP1, which limits induction of non-canonical NF-?B and activation of caspase-8. J. Biol. Chem. 286:13282-91
127. Kim JY, Morgan M, Kim DG, Lee JY, Bai L, et al. 2011. TNF?induced noncanonical NF-?B activation is attenuated by RIP1 through stabilization of TRAF2. J. Cell Sci. 124:647-56
128. Mandal P, Berger SB, Pillay S, Moriwaki K, Huang C, et al. 2014. RIP3 induces apoptosis independent of pronecrotic kinase activity. Mol. Cell 56:481-95
129. Lawlor KE, Khan N, Mildenhall A, Gerlic M, Croker BA, et al. 2015. RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nat. Commun. 6:6282
130. Moriwaki K, Bertin J, Gough PJ, Chan FK. 2015. A RIPK3-caspase 8 complex mediates atypical pro-IL-1?processing. J. Immunol. 194:1938-44
131. Tsutsui H, Kayagaki N, Kuida K, Nakano H, Hayashi N, et al. 1999. Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion frommacrophages causes acute liver injury in mice. Immunity 11:359-67
132. BossallerL, Chiang PI, Schmidt-LauberC, Ganesan S, Kaiser WJ, et al. 2012. Cutting edge: FAS (CD95) mediates noncanonical IL-1? and IL-18 maturation via caspase-8 in an RIP3-independent manner. J. Immunol. 189:5508-12
133. Vince JE, Wong WW, Gentle I, Lawlor KE, Allam R, et al. 2012. Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation. Immunity 36:215-27
134. Kang TB, Yang SH, Toth B, Kovalenko A, Wallach D. 2013. Caspase-8 blocks kinase RIPK3-mediated activation of the NLRP3 inflammasome. Immunity 38:27-40
135. YabalM, Muller N, Adler H, Knies N, Gross CJ, et al. 2014. XIAP restricts TNF-and RIP3-dependent cell death and inflammasome activation. Cell Rep. 7:1796-808
136. Wang X, JiangW, Yan Y, Gong T, Han J, et al. 2014. RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway. Nat. Immunol. 15:1126-33
137. Duong BH, OnizawaM, Oses-Prieto JA, AdvinculaR, Burlingame A, et al. 2015. A20 restricts ubiquitination of pro-interleukin-1?protein complexes and suppresses NLRP3 inflammasome activity. Immunity 42:55-67
138. Kang S, Fernandes-Alnemri T, Rogers C, Mayes L, Wang Y, et al. 2015. Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3. Nat. Commun. 6:7515
139. WongWW, Vince JE, Lalaoui N, Lawlor KE, ChauD, et al. 2014. cIAPs and XIAP regulatemyelopoiesis through cytokine production in an RIPK1-and RIPK3-dependent manner. Blood 123:2562-72
140. Rodriguez DA, Weinlich R, Brown S, Guy C, Fitzgerald P, et al. 2015. Characterization of RIPK3-mediated phosphorylation of the activation loop of MLKL during necroptosis. Cell Death Differ. 23:76-88
141. OnizawaM, Oshima S, Schulze-Topphoff U, Oses-Prieto JA, Lu T, et al. 2015. The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis. Nat. Immunol. 16:618-27
142. Lu TT, Onizawa M, Hammer GE, Turer EE, Yin Q, et al. 2013. Dimerization and ubiquitin mediated recruitment of A20, a complex deubiquitinating enzyme. Immunity 38:896-905
143. De A, Dainichi T, Rathinam CV, Ghosh S. 2014. The deubiquitinase activity of A20 is dispensable for NF-?B signaling. EMBO Rep. 15:775-83
144. Catrysse L, Vereecke L, Beyaert R, van Loo G. 2014. A20 in inflammation and autoimmunity. Trends Immunol. 35:22-31
145. Caenepeel S, Charydczak G, Sudarsanam S, Hunter T, Manning G. 2004. Themouse kinome: discovery and comparative genomics of all mouse protein kinases. PNAS 101:11707-12
146. Xie T, PengW, Yan C, Wu J, Gong X, Shi Y. 2013. Structural insights into RIP3-mediated necroptotic signaling. Cell Rep. 5:70-78
147. Kitur K, Parker D, Nieto P, Ahn DS, Cohen TS, et al. 2015. Toxin-induced necroptosis is a major mechanism of Staphylococcus aureus lung damage. PLOS Pathog. 11:e1004820