Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis

Trends in Pharmacological Sciences

Volumn 38, Issue 3, 2017, Pages 202-225

  Wegner, Kelby W ^a   Saleh, Danish ^b   Degterev, Alexei ^a  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b TUFTS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; HEAT SHOCK PROTEIN; HIGH MOBILITY GROUP B1 PROTEIN; PONATINIB; PROTEIN SERINE THREONINE KINASE; RECEPTOR PROTEIN; RECEPTOR PROTEIN INTERACTING KINASE 1; RECEPTOR PROTEIN INTERACTING KINASE 2; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNCLASSIFIED DRUG; URIC ACID; RECEPTOR INTERACTING PROTEIN SERINE THREONINE KINASE; RIPK1 PROTEIN, HUMAN; RIPK1 PROTEIN, MOUSE; RIPK3 PROTEIN, HUMAN; RIPK3 PROTEIN, MOUSE;

APOPTOSIS; CANCER CELL; CELL DEATH; CELL PROLIFERATION; CELLS BY BODY ANATOMY; CHRONIC INFLAMMATION; HUMAN; INFLAMMATION; MOUSE; NECROPTOSIS; NERVE FIBER DEGENERATION; NONHUMAN; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; STRUCTURE ACTIVITY RELATION; ANIMAL; ENZYMOLOGY; METABOLISM; NECROSIS;

ANIMALS; HUMANS; NECROSIS; RECEPTOR-INTERACTING PROTEIN SERINE-THREONINE KINASES;

EID: 85009962511     PISSN: 01656147     EISSN: 18733735     Source Type: Journal    
DOI: 10.1016/j.tips.2016.12.005     Document Type: Review

References (181)

1. 1 Thompson, C., Apoptosis in the pathogenesis and treatment of disease. Science 267 (1995), 1456–1462.
2. 2 Laster, S.M., et al. Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis. J. Immunol. 141 (1988), 2629–2634.
3. 3 Vercammen, D., et al. Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor. J. Exp. Med. 187 (1998), 1477–1485.
4. 4 Vercammen, D., et al. Tumour necrosis factor-induced necrosis versus anti-Fas-induced apoptosis in L929 cells. Cytokine 9 (1997), 801–808.
5. 5 Holler, N., et al. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat. Immunol. 1 (2000), 489–495.
6. 6 Matsumura, H., et al. Necrotic death pathway in Fas receptor signaling. J. Cell. Biol. 151 (2000), 1247–1256.
7. 7 Vanden Berghe, T., et al. Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features. Cell Death Differ. 17 (2010), 922–930.
8. 8 Chan, F.K., et al. A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. J. Biol. Chem. 278 (2003), 51613–51621.
9. 9 Degterev, A., et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat. Chem. Biol. 1 (2005), 112–119.
10. 10 Degterev, A., et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat. Chem. Biol. 4 (2008), 313–321.
11. 11 Kaczmarek, A., et al. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity 38 (2013), 209–223.
12. 12 Thapa, R.J., et al. Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), E3109–E3118.
13. 13 He, S., et al. Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 20054–20059.
14. 14 Upton, J.W., et al. Virus inhibition of RIP3-dependent necrosis. Cell Host Microbe 7 (2010), 302–313.
15. 15 Vanden Berghe, T., Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat. Rev. Mol. Cell Biol. 15 (2014), 135–147.
16. 16 Vanlangenakker, N., Many stimuli pull the necrotic trigger, an overview. Cell Death Differ. 19 (2012), 75–86.
17. 17 Micheau, O., Tschopp, J., Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114 (2003), 181–190.
18. 18 Wong, W.W., et al. RIPK1 is not essential for TNFR1-induced activation of NF-kappaB. Cell Death Differ. 17 (2010), 482–487.
19. 19 Varfolomeev, E., et al. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J. Biol. Chem. 283 (2008), 24295–24299.
20. 20 Gerlach, B., et al. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature 471 (2011), 591–596.
21. 21 Dondelinger, Y., et al. Poly-ubiquitination in TNFR1-mediated necroptosis. Cell Mol. Life Sci. 73 (2016), 2165–2176.
22. 22 Peltzer, N., et al. Holding RIPK1 on the ubiquitin leash in TNFR1 signaling. Trends Cell Biol. 26 (2016), 445–461.
23. 23 Justus, S.J., Ting, A.T., Cloaked in ubiquitin, a killer hides in plain sight: the molecular regulation of RIPK1. Immunol. Rev. 266 (2015), 145–160.
24. 24 Dickens, L.S., et al. The ‘complexities’ of life and death: death receptor signalling platforms. Exp. Cell Res. 318 (2012), 1269–1277.
25. 25 Dillon, C.P., et al. Survival function of the FADD-CASPASE-8-cFLIP(L) complex. Cell Rep. 1 (2012), 401–407.
26. 26 Moquin, D.M., et al. CYLD deubiquitinates RIP1 in the TNFalpha-induced necrosome to facilitate kinase activation and programmed necrosis. PLoS One, 8, 2013, e76841.
27. 27 O'Donnell, M.A., et al. Caspase 8 inhibits programmed necrosis by processing CYLD. Nat. Cell Biol. 13 (2011), 1437–1442.
28. 28 Legarda, D., et al. CYLD Proteolysis protects macrophages from TNF-mediated auto-necroptosis induced by LPS and licensed by Type I IFN. Cell Rep. 15 (2016), 2449–2461.
29. 29 Onizawa, M., et al. The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis. Nat. Immunol. 16 (2015), 618–627.
30. 30 Wertz, I.E., et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 430 (2004), 694–699.
31. 31 Bellail, A.C., et al. A20 ubiquitin ligase-mediated polyubiquitination of RIP1 inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma. Cancer Discov. 2 (2012), 140–155.
32. 32 Cho, Y.S., et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137 (2009), 1112–1123.
33. 33 Meng, L., et al. RIP3-mediated necrotic cell death accelerates systematic inflammation and mortality. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), 11007–11012.
34. 34 Ito, Y., et al. RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Science 353:6299 (2016), 603–608.
35. 35 Ofengeim, D., et al. Activation of necroptosis in multiple sclerosis. Cell Rep. 10 (2015), 1836–1849.
36. 36 Berger, S.B., et al. Cutting Edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice. J. Immunol. 192 (2014), 5476–5480.
37. 37 Najjar, M., et al. RIPK1 and RIPK3 kinases promote cell-death-independent inflammation by toll-like receptor 4. Immunity 45 (2016), 46–59.
38. 38 McQuade, T., et al. Positive and negative phosphorylation regulates RIP1- and RIP3-induced programmed necrosis. Biochem. J. 456 (2013), 409–415.
39. 39 Dondelinger, Y., et al. NF-kappaB-independent role of IKKalpha/IKKbeta in preventing RIPK1 kinase-dependent apoptotic and necroptotic cell death during TNF signaling. Mol. Cell 60 (2015), 63–76.
40. 40 O'Donnell, M.A., et al. NEMO inhibits programmed necrosis in an NFkappaB-independent manner by restraining RIP1. PLoS One, 7, 2012, e41238.
41. 41 Vlantis, K., et al. NEMO prevents RIP kinase 1-mediated epithelial cell death and chronic intestinal inflammation by NF-kappaB-dependent and -independent functions. Immunity 44 (2016), 553–567.
42. 42 Dondelinger, Y., et al. RIPK3 contributes to TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion or TAK1 kinase inhibition. Cell Death Differ. 20 (2013), 1381–1392.
43. 43 Vanlangenakker, N., cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell Death Differ. 18 (2011), 656–665.
44. 44 Blonska, M., et al. TAK1 is recruited to the tumor necrosis factor-alpha (TNF-alpha) receptor 1 complex in a receptor-interacting protein (RIP)-dependent manner and cooperates with MEKK3 leading to NF-kappaB activation. J. Biol. Chem. 280 (2005), 43056–43063.
45. 45 Kanayama, A., et al. TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. Mol. Cell 15 (2004), 535–548.
46. 46 Zhang, S.Q., et al. Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation. Immunity 12 (2000), 301–311.
47. 47 Wu, C.J., et al. Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected]. Nat. Cell Biol. 8 (2006), 398–406.
48. 48 de Almagro, M.C., et al. Coordinated ubiquitination and phosphorylation of RIP1 regulates necroptotic cell death. Cell Death Differ. 24 (2016), 26–37.
49. 49 Li, J., et al. The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell 150 (2012), 339–350.
50. 50 Chen, W., et al. 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 (2013), 16247–16261.
51. 51 Mandal, P., et al. RIP3 induces apoptosis independent of pronecrotic kinase activity. Mol. Cell 56 (2014), 481–495.
52. 52 Murphy, J.M., et al. The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 39 (2013), 443–453.
53. 53 Cook, W.D., et al. RIPK1- and RIPK3-induced cell death mode is determined by target availability. Cell Death Differ. 21 (2014), 1600–1612.
54. 54 Orozco, S., et al. RIPK1 both positively and negatively regulates RIPK3 oligomerization and necroptosis. Cell Death Differ. 21 (2014), 1511–1521.
55. 55 Wu, X.N., et al. Distinct roles of RIP1-RIP3 hetero- and RIP3-RIP3 homo-interaction in mediating necroptosis. Cell Death Differ. 21 (2014), 1709–1720.
56. 56 Su, L., et al. A plug release mechanism for membrane permeation by MLKL. Structure 22 (2014), 1489–1500.
57. 57 Sun, L., et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148 (2012), 213–227.
58. 58 Wang, H., et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol. Cell 54 (2014), 133–146.
59. 59 Wu, J., et al. Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis. Cell Res. 23 (2013), 994–1006.
60. 60 Cai, Z., et al. Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat. Cell Biol. 16 (2014), 55–65.
61. 61 Chen, X., et al. Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res. 24 (2014), 105–121.
62. 62 Dondelinger, Y., et al. MLKL compromises plasma membrane integrity by binding to phosphatidylinositol phosphates. Cell Rep. 7 (2014), 971–981.
63. 63 Quarato, G., et al. Sequential engagement of distinct MLKL phosphatidylinositol-binding sites executes necroptosis. Mol. Cell 61 (2016), 589–601.
64. 64 Hildebrand, J.M., et al. Flicking the molecular switch underlying MLKL-mediated necroptosis. Mol. Cell Oncol., 2, 2015, e985550.
65. 65 Degterev, A., Linkermann, A., Generation of small molecules to interfere with regulated necrosis. Cell Mol. Life Sci. 73 (2016), 2251–2267.
66. 66 Polykratis, A., et al. Cutting edge: RIPK1 Kinase inactive mice are viable and protected from TNF-induced necroptosis in vivo. J. Immunol. 193 (2014), 1539–1543.
67. 67 Kelliher, M.A., et al. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity 8 (1998), 297–303.
68. 68 Li, H., et al. Ubiquitination of RIP is required for tumor necrosis factor alpha-induced NF-kappaB activation. J. Biol. Chem. 281 (2006), 13636–13643.
69. 69 Newton, K., et al. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science 343 (2014), 1357–1360.
70. 70 Biton, S., Ashkenazi, A., NEMO and RIP1 control cell fate in response to extensive DNA damage via TNF-alpha feedforward signaling. Cell 145 (2011), 92–103.
71. 71 Christofferson, D.E., A novel role for RIP1 kinase in mediating TNFalpha production. Cell Death Dis., 3, 2012, e320.
72. 72 Hitomi, J., et al. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell 135 (2008), 1311–1323.
73. 73 McNamara, C.R., et al. Akt regulates TNFalpha synthesis downstream of RIP1 kinase activation during necroptosis. PLoS One, 8, 2013, e56576.
74. 74 Wong, W.W., et al. cIAPs and XIAP regulate myelopoiesis through cytokine production in an RIPK1- and RIPK3-dependent manner. Blood 123 (2014), 2562–2572.
75. 75 Dillon, C.P., et al. RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3. Cell 157 (2014), 1189–1202.
76. 76 Upton, J.W., et al. DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host Microbe 11 (2012), 290–297.
77. 77 Kaiser, W.J., et al. RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 7753–7758.
78. 78 Takahashi, N., et al. RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis. Nature 513 (2014), 95–99.
79. 79 Rickard, J.A., et al. RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. Cell 157 (2014), 1175–1188.
80. 80 Dannappel, M., et al. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 513 (2014), 90–94.
81. 81 Kearney, C.J., et al. Necroptosis suppresses inflammation via termination of TNF- or LPS-induced cytokine and chemokine production. Cell Death Differ. 22 (2015), 1313–1327.
82. 82 Gunther, C., et al. The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis. J. Clin. Invest. 126 (2016), 4346–4360.
83. 83 Newton, K., et al. RIPK3 deficiency or catalytically inactive RIPK1 provides greater benefit than MLKL deficiency in mouse models of inflammation and tissue injury. Cell Death Differ. 23 (2016), 1565–1576.
84. 84 Nogusa, S., et al. RIPK3 activates parallel pathways of MLKL-driven necroptosis and FADD-mediated apoptosis to protect against influenza A virus. Cell Host Microbe 20 (2016), 13–24.
85. 85 Moriwaki, K., et al. A RIPK3-caspase 8 complex mediates atypical pro-IL-1beta processing. J. Immunol. 194 (2015), 1938–1944.
86. 86 Moriwaki, K., et al. The necroptosis adaptor RIPK3 promotes injury-induced cytokine expression and tissue repair. Immunity 41 (2014), 567–578.
87. 87 Moriwaki, K., et al. Border security: the role of RIPK3 in epithelium homeostasis. Front. Cell Dev. Biol., 4, 2016, 70.
88. 88 Lawlor, K.E., et al. RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nat. Commun., 6, 2015, 6282.
89. 89 Vince, J.E., et al. Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation. Immunity 36 (2012), 215–227.
90. 90 Degterev, A., et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat. Chem. Biol. 1 (2005), 112–119.
91. 91 Zhou, W., Yuan, J., Necroptosis in health and diseases. Semin. Cell Dev. Biol. 35 (2014), 14–23.
92. 92 Smith, C.C., et al. Necrostatin: a potentially novel cardioprotective agent?. Cardiovasc. Drugs Ther. 21 (2007), 227–233.
93. 93 Oerlemans, M.I., et al. Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia-reperfusion in vivo. Basic Res. Cardiol., 107, 2012, 270.
94. 94 Koudstaal, S., et al. Necrostatin-1 alleviates reperfusion injury following acute myocardial infarction in pigs. Eur. J. Clin. Invest. 45 (2015), 150–159.
95. 95 Luedde, M., et al. RIP3, a kinase promoting necroptotic cell death, mediates adverse remodelling after myocardial infarction. Cardiovasc. Res. 103 (2014), 206–216.
96. 96 Zhang, T., et al. CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis. Nat. Med. 22 (2016), 175–182.
97. 97 Wang, Z., et al. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell 148 (2012), 228–243.
98. 98 Moriwaki, K., et al. The mitochondrial phosphatase PGAM5 is dispensable for necroptosis but promotes inflammasome activation in macrophages. J. Immunol. 196 (2016), 407–415.
99. 99 Lu, W., et al. Mitochondrial protein PGAM5 regulates mitophagic protection against cell necroptosis. PLoS One, 11, 2016, e0147792.
100. 100 Chen, G., et al. A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy. Mol. Cell 54 (2014), 362–377.
101. 101 Duprez, L., et al. RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome. Immunity 35 (2011), 908–918.
102. 102 Grewal, I.S., Overview of TNF superfamily: a chest full of potential therapeutic targets. Adv. Exp. Med. Biol. 647 (2009), 1–7.
103. 103 Pierdomenico, M., Necroptosis is active in children with inflammatory bowel disease and contributes to heighten intestinal inflammation. Am. J. Gastroenterol. 109 (2014), 279–287.
104. 104 Liu, Z.Y., et al. Necrostatin-1 reduces intestinal inflammation and colitis-associated tumorigenesis in mice. Am. J. Cancer Res. 5 (2015), 3174–3185.
105. 105 Kondylis, V., et al. NEMO prevents steatohepatitis and hepatocellular carcinoma by inhibiting RIPK1 kinase activity-mediated hepatocyte apoptosis. Cancer Cell 28 (2015), 582–598.
106. 106 Lukens, J.R., et al. RIP1-driven autoinflammation targets IL-1alpha independently of inflammasomes and RIP3. Nature 498 (2013), 224–227.
107. 107 Meng, L., et al. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis. Biochem. Biophys. Res. Commun. 473 (2016), 497–502.
108. 108 Rickard, J.A., et al. TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice. Elife, 3, 2014, 03464.
109. 109 Boisson, B., et al. Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia. J. Exp. Med. 212 (2015), 939–951.
110. 110 Boisson, B., et al. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat. Immunol. 13 (2012), 1178–1186.
111. 111 Re, D.B., et al. Necroptosis drives motor neuron death in models of both sporadic and familial ALS. Neuron 81 (2014), 1001–1008.
112. 112 Zhang, X., et al. MLKL and FADD are critical for suppressing progressive lymphoproliferative disease and activating the NLRP3 inflammasome. Cell Rep. 16 (2016), 3247–3259.
113. 113 Alvarez-Diaz, S., The pseudokinase MLKL and the kinase RIPK3 have distinct roles in autoimmune disease caused by loss of death-receptor-induced apoptosis. Immunity 45 (2016), 513–526.
114. 114 Lee, E.G., et al. Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science 289 (2000), 2350–2354.
115. 115 Zhou, Q., et al. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease. Nat. Genet. 48 (2016), 67–73.
116. 116 Moriwaki, K., Chan, F.K., Necroptosis-independent signaling by the RIP kinases in inflammation. Cell Mol. Life Sci. 73 (2016), 2325–2334.
117. 117 Han, W., et al. Shikonin circumvents cancer drug resistance by induction of a necroptotic death. Mol. Cancer Ther. 6 (2007), 1641–1649.
118. 118 Lehne, G., P-glycoprotein as a drug target in the treatment of multidrug resistant cancer. Curr. Drug Targets 1 (2000), 85–99.
119. 119 Huang, C., et al. Shikonin kills glioma cells through necroptosis mediated by RIP-1. PLoS One, 8, 2013, e66326.
120. 120 Shahsavari, Z., et al. Shikonin induced necroptosis via reactive oxygen species in the T-47D breast cancer cell line. Asian Pac. J. Cancer Prev. 16 (2015), 7261–7266.
121. 121 Fu, Z., et al. The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3 dependent necroptosis. BMC Cancer, 13, 2013, 580.
122. 122 Wada, N., et al. Shikonin, dually functions as a proteasome inhibitor and a necroptosis inducer in multiple myeloma cells. Int. J. Oncol. 46 (2015), 963–972.
123. 123 Tenev, T., et al. The ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol. Cell. 43 (2011), 432–448.
124. 124 Feoktistova, M., et al. cIAPs block ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol. Cell 43 (2011), 449–463.
125. 125 Najjar, M., et al. Structure guided design of potent and selective ponatinib-based hybrid inhibitors for RIPK1. Cell Rep. 10 (2015), 1850–1860.
126. 126 Li, L., et al. A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science 305 (2004), 1471–1474.
127. 127 Varfolomeev, E., et al. IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell 131 (2007), 669–681.
128. 128 Vince, J.E., et al. IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis. Cell 131 (2007), 682–693.
129. 129 Bake, V., et al. Synergistic interaction of Smac mimetic and IFNalpha to trigger apoptosis in acute myeloid leukemia cells. Cancer Lett. 355 (2014), 224–231.
130. 130 Cristofanon, S., et al. Identification of RIP1 as a critical mediator of Smac mimetic-mediated sensitization of glioblastoma cells for drozitumab-induced apoptosis. Cell Death Dis., 6, 2015, e1724.
131. 131 Czaplinski, S., et al. Differential role of RIP1 in Smac mimetic-mediated chemosensitization of neuroblastoma cells. Oncotarget 6 (2015), 41522–41534.
132. 132 Fulda, S., et al. Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat. Med. 8 (2002), 808–815.
133. 133 Hehlgans, S., et al. The SMAC mimetic BV6 sensitizes colorectal cancer cells to ionizing radiation by interfering with DNA repair processes and enhancing apoptosis. Radiat. Oncol., 10, 2015, 198.
134. 134 Liese, J., et al. Smac mimetic and oleanolic acid synergize to induce cell death in human hepatocellular carcinoma cells. Cancer Lett. 365 (2015), 47–56.
135. 135 Lueck, S.C., et al. Smac mimetic induces cell death in a large proportion of primary acute myeloid leukemia samples, which correlates with defined molecular markers. Oncotarget 7 (2016), 49539–49551.
136. 136 Opel, D., et al. Targeting inhibitor of apoptosis proteins by Smac mimetic elicits cell death in poor prognostic subgroups of chronic lymphocytic leukemia. Int. J. Cancer 137 (2015), 2959–2970.
137. 137 Schenk, B., Fulda, S., Reactive oxygen species regulate Smac mimetic/TNFalpha-induced necroptotic signaling and cell death. Oncogene 34 (2015), 5796–5806.
138. 138 Seyfrid, M., et al. Reactive oxygen species contribute toward Smac mimetic/temozolomide-induced cell death in glioblastoma cells. Anticancer Drugs 27 (2016), 953–959.
139. 139 Steinwascher, S., Identification of a novel synergistic induction of cell death by Smac mimetic and HDAC inhibitors in acute myeloid leukemia cells. Cancer Lett. 366 (2015), 32–43.
140. 140 Wagner, L., et al. Smac mimetic sensitizes glioblastoma cells to temozolomide-induced apoptosis in a RIP1- and NF-kappaB-dependent manner. Oncogene 32 (2013), 988–997.
141. 141 Brumatti, G., et al. The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia. Sci. Transl. Med., 8, 2016, 339ra69.
142. 142 Hannes, S., et al. Smac mimetic triggers necroptosis in pancreatic carcinoma cells when caspase activation is blocked. Cancer Lett. 380 (2016), 31–38.
143. 143 McComb, S., et al. Activation of concurrent apoptosis and necroptosis by SMAC mimetics for the treatment of refractory and relapsed ALL. Sci. Transl. Med., 8, 2016, 339ra70.
144. 144 Koo, G.B., et al. Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics. Cell Res. 25 (2015), 707–725.
145. 145 Gerges, S., et al. Cotreatment with Smac mimetics and demethylating agents induces both apoptotic and necroptotic cell death pathways in acute lymphoblastic leukemia cells. Cancer Lett. 375 (2016), 127–132.
146. 146 Steinhart, L., et al. Smac mimetic and demethylating agents synergistically trigger cell death in acute myeloid leukemia cells and overcome apoptosis resistance by inducing necroptosis. Cell Death Dis., 4, 2013, e802.
147. 147 Lindemann, C., et al. Smac Mimetic-Induced Upregulation of CCL2/MCP-1 triggers migration and invasion of glioblastoma cells and influences the tumor microenvironment in a paracrine manner. Neoplasia 17 (2015), 481–489.
148. 148 Rettinger, E., et al. SMAC mimetic BV6 enables sensitization of resistant tumor cells but also affects cytokine-induced killer (CIK) cells: a potential challenge for combination therapy. Front. Pediatr., 2, 2014, 75.
149. 149 Seifert, L., et al. The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression. Nature 532 (2016), 245–249.
150. 150 Liu, X., et al. Key roles of necroptotic factors in promoting tumor growth. Oncotarget 7 (2016), 22219–22233.
151. 151 Tortola, L., et al. The tumor suppressor hace1 is a critical regulator of TNFR1-mediated cell fate. Cell Rep. 15 (2016), 1481–1492.
152. + T cells. Science 350 (2015), 328–334.
153. 153 Aaes, T.L., et al. Vaccination with necroptotic cancer cells induces efficient anti-tumor immunity. Cell Rep. 15 (2016), 274–287.
154. 154 Schmidt, S.V., et al. RIPK3 expression in cervical cancer cells is required for PolyIC-induced necroptosis, IL-1alpha release, and efficient paracrine dendritic cell activation. Oncotarget 6 (2015), 8635–8647.
155. 155 Zou, J., et al. Poly IC triggers a cathepsin D- and IPS-1-dependent pathway to enhance cytokine production and mediate dendritic cell necroptosis. Immunity 38 (2013), 717–728.
156. 156 Zou, C., et al. Design, synthesis, and biological evaluation of 1-Benzyl-1H-pyrazole derivatives as receptor interacting protein 1 kinase inhibitors. Chem. Biol. Drug Des. 87 (2016), 569–574.
157. 157 Degterev, A., et al. Activity and specificity of necrostatin-1, small-molecule inhibitor of RIP1 kinase. Cell Death Differ., 20, 2013, 366.
158. 158 Berger, S.B., et al. Characterization of GSK’963: a structurally distinct, potent and selective inhibitor of RIP1 kinase. Cell Death Discov., 1, 2015, 15009.
159. 159 Harris, P.A., et al. DNA-encoded library screening identifies benzo[b][1,4]oxazepin-4-ones as highly potent and monoselective receptor interacting protein 1 kinase inhibitors. J. Med. Chem. 59 (2016), 2163–2178.
160. 160 Xie, T., et al. Structural basis of RIP1 inhibition by necrostatins. Structure 21 (2013), 493–499.
161. 161 Yang, C.K., He, S.D., Heat shock protein 90 regulates necroptosis by modulating multiple signaling effectors. Cell Death Dis., 7, 2016, e2126.
162. 162 Jacobsen, A.V., et al. HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death. Cell Death Dis., 7, 2016, e2051.
163. 163 Li, D., et al. Natural product kongensin A is a non-canonical HSP90 inhibitor that blocks RIP3-dependent necroptosis. Cell Chem. Biol. 23 (2016), 257–266.
164. 164 Han, W., et al. Necrostatin-1 reverts shikonin-induced necroptosis to apoptosis. Apoptosis 14 (2009), 674–686.
165. 165 Jie, H., et al. Necrostatin-1 enhances the resolution of inflammation by specifically inducing neutrophil apoptosis. Oncotarget 7 (2016), 19367–19381.
166. 166 Pasparakis, M., Vandenabeele, P., Necroptosis and its role in inflammation. Nature 517 (2015), 311–320.
167. 167 Silke, J., et al. The diverse role of RIP kinases in necroptosis and inflammation. Nat. Immunol. 16 (2015), 689–697.
168. 168 Dillon, C.P., et al. Developmental checkpoints guarded by regulated necrosis. Cell Mol. Life Sci. 73 (2016), 2125–2136.
169. 169 Weinlich, R., et al. Protective roles for caspase-8 and cFLIP in adult homeostasis. Cell Rep. 5 (2013), 340–348.
170. 170 Xie, T., et al. Structural insights into RIP3-mediated necroptotic signaling. Cell Rep. 5 (2013), 70–78.
171. 171 Jagtap, P.G., et al. Structure-activity relationship study of tricyclic necroptosis inhibitors. J. Med. Chem. 50 (2007), 1886–1895.
172. 172 Teng, X., et al. Structure-activity relationship study of [1,2,3]thiadiazole necroptosis inhibitors. Bioorg. Med. Chem. Lett. 17 (2007), 6836–6840.
173. 173 Teng, X., et al. Structure-activity relationship and liver microsome stability studies of pyrrole necroptosis inhibitors. Bioorg. Med. Chem. Lett. 18 (2008), 3219–3223.
174. 174 Wang, K., et al. Structure-activity relationship analysis of a novel necroptosis inhibitor, necrostatin-5. Bioorg. Med. Chem. Lett. 17 (2007), 1455–1465.
175. 175 Teng, X., et al. Structure-activity relationship study of novel necroptosis inhibitors. Bioorg. Med. Chem. Lett. 15 (2005), 5039–5044.
176. 176 Harris, P.A., et al. Discovery of small molecule RIP1 kinase inhibitors for the treatment of pathologies associated with necroptosis. ACS Med. Chem. Lett. 4 (2013), 1238–1243.
177. 177 Fauster, A., et al. A cellular screen identifies ponatinib and pazopanib as inhibitors of necroptosis. Cell Death Dis., 6, 2015, e1767.
178. 178 Kaiser, W.J., et al. Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL. J. Biol. Chem. 288 (2013), 31268–31279.
179. 179 Rodriguez, D.A., et al. Characterization of RIPK3-mediated phosphorylation of the activation loop of MLKL during necroptosis. Cell Death Differ. 23 (2016), 76–88.
180. 180 Li, J.X., et al. The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury. Cell Death Dis., 5, 2014, e1278.
181. 181 Hildebrand, J.M., et al. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 15072–15077.