Skip to main content
Log in

Abstract

Out of the almost 17 members of the TNF superfamily, TNF is probably the most potent inducer of apoptosis. TNF activates both cell-survival and cell-death mechanisms simultaneously. Activation of NF-kB-dependent genes regulates the survival and proliferative effects pf TNF, whereas activation of caspases regulates the apoptotic effects. TNF-induced apoptosis is mediated primarily through the activation of type I receptors, the death domain of which recruits more than a dozen different signaling proteins, which together are considered part of an apoptotic cascade. This cascade does not, however, account for the role of reactive oxygen intermediates, ceramide, phospholipases, and serine proteases which are also inplicated in TNF-induced apoptosis. This cascade also does not explain how type II TNF receptors which lack the death domain, induce apoptosis. Nevertheless, this review of apoptosis signaling will be limited to those proteins that makeup the cascade.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

REFERENCES

  1. Wyllie A, Kerr J, Currie A: Cell death: The significance of apoptosis. Int Rev Cytol 68:251–306, 1980.

    Google Scholar 

  2. Tewari M, Quan LT. O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM: Yama/CPP32b, a mammalian homolog of CED-3, is a crmA-inhibitable protease that cleaves the death substrate poly (ADP-ribose) polymerase. Cell 81:801–809, 1995

    Google Scholar 

  3. Prasad KVS, Ao Z, Yoon Y, Wu MX, Rizk M, Jacqoat S, Schlossman SF: CD27, a member of the tumor necrosis factor receptor family, induces apotposis and binds to Siva, a proapoptotic protein. Proc Natl Acad Sci USA 94:6346–6351, 1997

    Google Scholar 

  4. Han DK, Chaudhury PM, Wright ME, Freidman C, Trask BJ, Riedel RT, Baskin DG, Schwartz SM, Hood L: MRIT, a novel death effector domain-containing protein, interacts with caspases and BclXL and initiates cell death. Proc Natl Acad Sci USA 94:11333–11338, 1997

    Google Scholar 

  5. Aggarwal BB, Vilcek J (eds): Tumor Necrosis Factors: Structure, Function and Mechanism of Action. New York, Marcel Dekker, 1992

    Google Scholar 

  6. Sidoti-de Fraisse C, Rincheval V, Risler Y, Mignotte B, Vayssiere JL: TNF activates at least two apoptotic signaling cascades. Oncogene 17:1639–1651, 1998

    Google Scholar 

  7. Natoli G, Costanzo A, Guido F, Moretti F, Levrero M: Apoptotic, non-apoptotic, and anti-apoptotic pathways of tumor necrosis factor signalling. Biochem Pharmacol 56:915–920, 1998

    Google Scholar 

  8. Burow ME, Weldon CB, Tang Y, Navar GL, Krajewski S, Reed JC, Hammond TG, Clejan S, Beckman BS: Differences in susceptibility to tumor necrosis factor-α-induced apoptosis among MCF-7 breast cancer cell variants. Cancer Res 58:4940–4946, 1998

    Google Scholar 

  9. Vandanabeele PW, Declercq R, Beyaert, Fiers W: Two tumor necrosis factor receptors: structure and function. Trends Cell Biol 5:392, 1995

    Google Scholar 

  10. Cleveland JL, Ihle JN: Contenders in FasL/TNF death signaling. Cell 81:479–482, 1995

    Google Scholar 

  11. Leist M, Gantner F, Jilg S, Wendel A: Activation of the 55 kDa TNF receptor is necessary and sufficient for TNF-induced liver failure, hepatocyte apoptosis, and nitrite release. J Immunol 154:1307–1316, 1995

    Google Scholar 

  12. Heller RA, Kronke M: Tumor necrosis factor receptor-mediated signaling pathways. J Cell Biol 126:5–9, 1994

    Google Scholar 

  13. Haridas V, Darnay BG, Natarajan K, Heller R, Aggarwal BB: Overexpression of the p80 TNF receptor leads to TNF-dependent apoptosis, nuclear factor-kappa B activation, and c-Jun kinase activation. J Immunol 160:3152–3162, 1998

    Google Scholar 

  14. Sipe KJ, Dantzer R, Kelley KW, Weyhenmeyer JA: Expression of the 75 kDA TNF receptor and its role in contact-mediated neuronal cell death. Mol Brain Res 62:111–121, 1998

    Google Scholar 

  15. Lucas R, Garcia I, Donati YR, Hribar M, Mandriota SJ, Giroud C, Buurman WA, Fransen L, Suter PM, Nunez G, Pepper MS, Grau GE: Both TNF receptors are required for direct TNF-mediated cytotoxicity in microvascular endothelial cells. Eur J Immunol 28:3577–3586, 1998

    Google Scholar 

  16. Vandenabeele P, Declercq W, Vanhaescebroeck B, Grooten J, Fiers W: Both TNF receptors are required for TNF-mediated induction of apoptosis in PC60 cells. J Immunol 154:2904–2913, 1995

    Google Scholar 

  17. Murray J, Barbara JA, Dunkley SA, Lopez AF, Van Ostade X, Condliffe AM, Dransfield I, Haslett C, Chilvers ER: Regulation of neutrophil apoptosis by tumor necrosis factor-alpha: Requirement for TNFR55 and TNFR75 for induction of apoptosis in vitro. Blood 90:2772–2783, 1997

    Google Scholar 

  18. Gon S, Gatanaga T, Sendo F: Involvement of two types of TNF receptor in TNF-alpha induced neutrophil apoptosis. Microbiol Immunol 40:463–465, 1996

    Google Scholar 

  19. Grell M, Douni E, Wajant H, Lohden M, Clauss M, Maxeiner B, Georgopoulos S, Lesslauer W, Kollias G, Pfizenmaier K, et al.: The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell 83:793–802, 1995

    Google Scholar 

  20. McDermott MF, et al.: Germ line mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 9:133–144, 1999

    Google Scholar 

  21. Polunovsky VA, Wendt CH, Ingbar DH, Peterson MS, Bitterman PB: Induction of endothelial cell apoptosis by TNF: Modulation by inhibitors of protein synthesis. Exp Cell Res 214:584–594, 1994

    Google Scholar 

  22. Krosnick JA, Mule JJ, McIntosh JK, Rosenberg SA: Augmentation of antitumor efficacy by the combination of recombinant tumor necrosis factor and chemotherapeutic agents in vivo. Cancer Res 49:3729–3733, 1989

    Google Scholar 

  23. Kobayashi D, Watanabe N, Yamauchi N, Tsuji N, Sato T, Sasaki H, Okamoto T, Niitsu Y: Protein kinase C inhibitors augment tumor-necrosis-factor-induced apoptosis in normal human diploid cells. Chemotherapy 43:415–423, 1997

    Google Scholar 

  24. Garcia-Lloret MI, Yui J, Winkler-Lowen B, Guilbert LJ: Epidermal growth factor inhibits cytokine-induced apoptosis of primary human trophoblasts. J Cell Physiol 167:324–332, 1996

    Google Scholar 

  25. Gardner AM, Johnson GL: Fibroblast growth factor-2 suppression of tumor necrosis factor alpha-mediated apoptosis requires Ras and the activation of mitogen-activated protein kinase. J Biol Chem 271:14560–14566, 1996

    Google Scholar 

  26. Wu Y, Tewari M, Cui S, Rubin R: Activation of the insulin-like growth factor-I receptor inhibits tumor necrosis factor-induced cell death. J Cell Physiol 168:499–509, 1996

    Google Scholar 

  27. Reinartz J, Bechtel MJ, Kramer MD: Tumor necrosis factor-alpha-induced apoptosis in a human keratinocyte cell line (HaCaT) is counteracted by transforming growth factor-alpha. Exp Cell Res 228:334–340, 1996

    Google Scholar 

  28. Chang NS, Mattison J, Cao H, Pratt N, Zhao Y, Lee C: Cloning and characterization of a novel transforming growth factor-beta 1-induced TIAF1 protein that inhibits tumor necrosis factor cytotoxicity. Biochem Biophys Res Commun 253:743–749, 1998

    Google Scholar 

  29. Senaldi G, Shaklee CL, Simon B, Rowan CG, Lacey DL, Hartung T: Keratinocyte growth factor protects murine hepatocytes from tumor necrosis factor-induced apoptosis in vivo and in vitro. Hepatology 27:1584–1591, 1998

    Google Scholar 

  30. Kothny-Wilkes G, Kulms D, Poppelmann B, Luger TA, Kubin M, Schwarz T: Interleukin-1 protects transformed keratinocytes from tumor necrosis factor-related apoptosis-inducing ligand. J Biol Chem 273:29247–29253, 1998

    Google Scholar 

  31. Manna SK, Aggarwal BB: Interleukin-4 down regulates both forms of tumor necrosis factor receptor and receptor mediated apoptosis, NF-kB, AP-1 and c-Jun N terminal kinase comparison with interleukin-13. J Biol Chem 273:33333–33341, 1998

    Google Scholar 

  32. Manna SK, Aggarwal BB: IL-13 suppresses TNF-induced activation of nuclear factor-kappa B, activation protein-1, and apoptosis. J Immunol 161:2863–2872, 1998

    Google Scholar 

  33. Hess S, Gottfried E, Smola H, Grunwald U, Schuchmann M, Engelmann H: CD40 induces resistance to TNF-mediated apoptosis in a fibroblast cell line. Eur J Immunol 28:3594–3604, 1998

    Google Scholar 

  34. Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS Jr: NFkappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to supress caspase 8 activation. Science 281:1680–1683, 1998

    Google Scholar 

  35. Chu ZL, McKinsey TA, Liu L, Gentry JJ, Malim MH, Ballard DW: Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-kappaB control. Proc Natl Acad Sci USA 94:10057–10062, 1997

    Google Scholar 

  36. Jaattela M, Benedict M, Tewari M, Shayman JA, Dixit VM: Bcl-x and Bcl-2 inhibit TNF and Fas-induced apoptosis and activation of phospholipase A2 in breast carcinoma cells. Oncogene 10:2297–2305, 1995

    Google Scholar 

  37. Genestier L, Bonnefoy-Berard N, Rouault JP, Flacher M, Revillard JP: Tumor necrosis factor-alpha up-regulates Bcl-2expression and decreases calcium-dependent apoptosis in human B cell lines. Int Immunol 7:533–540, 1995

    Google Scholar 

  38. Chen M, Quintans J, Fuks Z, Thompson C, Kufe DW, Weichselbaum RR: Suppression of Bcl-2 messenger RNA production may mediate apoptosis after ionizing radiation, tumor necrosis factor alpha, and ceramide. Cancer Res 55:991–994, 1995

    Google Scholar 

  39. Opipari AW Jr, Hu HM, Yabkowitz R, Dixit VM: The A20 zinc finger protein protects cells from tumor necrosis factor cytotoxicity. J Biol Chem 267:12424–12427, 1992

    Google Scholar 

  40. Wissing D, Mouritzen H, Jaattela M: TNF-induced mitochondrial es and activation of apoptotic proteases are inhibited by A20. Free Radical Biol Med 25:57–65, 1998

    Google Scholar 

  41. Okura T, Gong L, Kamitani T, Wada T, Okura I, Wei CF, Chang HM, Yeh ET: Protection against Fas/APO-1-and tumor necrosis factor-mediated cell death by a novel protein, sentrin. J Immunol 157:4277–4281, 1996

    Google Scholar 

  42. Wong GH, Elwell JH, Oberley LW, Goeddel DV: Manganous superoxide dismutase is essential for cellular resistance to cytotoxicity of tumor necrosis factor. Cell 58:923–931, 1989

    Google Scholar 

  43. Manna SK, Zhang HJ, Yan T, Oberley LW, Aggarwal BB: Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappaB and activated protein-1. J Biol Chem 273:13245–13254, 1998

    Google Scholar 

  44. Kim YM, de Vera ME, Watkins SC, Billiar TR: Nitric oxide protects cultured rat hepatocytes from tumor necrosis factor-alpha-induced apoptosis by inducing heat shock protein 70 expression. J Biol Chem 272:1402–1411, 1997

    Google Scholar 

  45. Heneka MT, Loschmann PA, Gleichmann M, Weller M, Schulz JB, Wullner U, Klockgether T: Induction of nitric oxide synthase and nitric oxide-mediated apoptosis in neuronal PC12 cells after stimulation with tumor necrosis factor-alpha/lipopolysaccharide. J Neurochem 71:88–94, 1998

    Google Scholar 

  46. Manna SK, Kuo MT, Aggarwal BB: Overexpression of γ-glutamylcysteine synthetase abolishes tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappa B and activator protein-1. Oncogene 18:4371–4382, 1999

    Google Scholar 

  47. Binder C, Binder L, Kroemker M, Schulz M, Hiddemann W: Influence of cycloheximide-mediated downregulation of glucose transport on TNF alpha-induced apoptosis. Exp Cell Res 236:223–230, 1997

    Google Scholar 

  48. Jiang Y, Porter AG: Prevention of tumor necrosis factor (TNF)-mediated induction of P21WAF1/CIP1 sensitizes MCF-7 carcinoma cells to TNF-induced apoptosis. Biochem Biophys Res Commun 245:691–697, 1998

    Google Scholar 

  49. Stehlik C, de Martin R, Kumabashiri I, Schmid JA, Binder BR, Lipp J: Nuclear factor (NF)-kappaB-regulated X-chromosomelinked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis. J Exp Med 188:211–216, 1998

    Google Scholar 

  50. Wu MX, Ao Z, Prasad KV, Wu R, Schlossman SF: IEX-1L, an apoptosis inhibitor involved in NF-kappaB-mediated cell survival. Science 281:998–1001, 1998

    Google Scholar 

  51. Jaattela M, Wissing D, Bauer PA, Li GC: Major heat shock protein hsp 70 protects tumor cells from tumor necrosis factor cytotoxicity. EMBO J 11:3507–3512, 1992

    Google Scholar 

  52. Karsan A, Yee E, Harlan JM: Endothelial cell death induced by tumor necrosis factor-alpha is inhibited by the Bcl-2 family member, A1. J Biol Chem 271:27201–27204, 1996

    Google Scholar 

  53. Dickinson JL, Bates EJ, Ferrante A, Antalis TM: Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor alpha-induced apoptosis. Evidence for an alternate biological function. J Biol Chem 270:27894–27904, 1995

    Google Scholar 

  54. Zong WX, Farrell M, Bash J, Gelinas C: v-Rel prevents apoptosis in transformed lymphoid cells and blocks TNF-induced cell death. Oncogene 15:971–980, 1997

    Google Scholar 

  55. Krajcsi P, Dimitrov T, Hermiston TW, Tollefson AE, Ranheim TS, Vande Pol SB, Stephenson AH, Wold WS: The adenovirus E3–14.7K protein and the E3–10.4K/14.5K complex of proteins, which independently inhibit tumor necrosis factor (TNF)-induced apoptosis, also independently inhibit TNF-induced release of arachidonic acid. J Virol 70:4904–4913, 1996

    Google Scholar 

  56. Hayakawa M, Ishida N, Takeuchi K, Shibamoto S, Hori T, Oku N, Ito F, Tsujimoto M: Arachidonic acid-selective cytosolic phospholipase A2 is crucial in the cytotoxic action of tumor necrosis factor. J Biol Chem 268:11290–11295, 1993

    Google Scholar 

  57. Jayadev S, Hayter HL, Andrieu N, Gamard CJ, Liu B, Balu R, Hayakawa M, Ito F, Hannun YA: Phospholipase A2 is necessary for tumor necrosis factor alpha-induced ceramide generation in L929 cells. J Biol Chem 272:17196–17203, 1997

    Google Scholar 

  58. Wu YL, Jiang XR, Newland AC, Kelsey SM: Failure to activate cytosolic phospholipase A2 causes TNF resistance in human leukemic cells. J Immunol 160:5929–5935, 1998

    Google Scholar 

  59. Mutch DG, Powell CB, Kao MS, Collins JL: Resistance to cytolysis by tumor necrosis factor alpha in malignant gynecological cell lines is associated with the expression of protein(s) that prevent the activation of phospholipase A2 by tumor necrosis factor alpha. Cancer Res 52:866–872, 1992

    Google Scholar 

  60. Wu YL, Jiang XR, Lillington DM, Allen PD, Newland AC, Kelsey SM: 1,25-Dihydroxyvitamin D3 protects human leukemic cells from tumor necrosis factor-induced apoptosis via inactivation of cytosolic phospholipase A2. Cancer Res 58:633–640, 1998

    Google Scholar 

  61. Rapp L, Liu Y, Hong Y, Androphy EJ, Chen JJ: The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis. Oncogene 18:607–615, 1999

    Google Scholar 

  62. Koloesnik R, Golde DW: The sphingomyelin pathway in tumor necrosis factor and interleukin-1 signaling. Cell 77:325–328, 1994

    Google Scholar 

  63. Kolesnick RN, Haimovitz-Friedman A, Fuks Z: The sphingomyelin signal transduction pathway mediates apoptosis for tumor necrosis factor, Fas, and ionizing radiation. Biochem Cell Biol 72:471–474, 1994

    Google Scholar 

  64. Obeid LM, Linardic CM, Karolak LA, Hannun YA: Programmed cell death induced by ceramide. Science 259:1769–1771, 1993

    Google Scholar 

  65. Wiegmann K, Schutze S, Machleidt T, Witte D, Kronke M: Functional dichotomy of neutral and acidic spingomyelinases in tumor necrosis factor signaling. Cell 78:1005–1015, 1994

    Google Scholar 

  66. Hofmann K, Dixit VM: Ceramide in apoptosis—Does it really matter? Trends Biochem Sci 23:374–377, 1998

    Google Scholar 

  67. Higuchi M, Singh S, Jaffrezou J-P, Aggarwal BB: Acidic sphingomyelinase-generated ceramide is needed but not sufficient for tumor necrosis factor-induced apoptosis and NF-κB activation. J Immunol 156:297–304, 1996

    Google Scholar 

  68. Xu Y, Jones BE, Neufeld DS, Czaja MJ: Glutathione modulates rat and mouse hepatocyte sensitivity to tumor necrosis factor toxicity. Gastroenterology 115:1229–1237, 1998

    Google Scholar 

  69. Ko YG, Lee JS, Kang YS, Ahn JH, Seo JS: TNF-alpha-mediated apoptosis is initiated in caveolae-like domains. J Immunol 162:7217–7223, 1999

    Google Scholar 

  70. Adam D, Wiegmann K, Adam-Klages S, Ruff A, Kronke M: A novel cytoplasmic domain of the p55 tumor necrosis factor receptor initiates the neutral sphingomyelinase pathway. J Biol Chem 271:14617–14622, 1996

    Google Scholar 

  71. Adam-Klages S, Adam D, Wiegmann K, Struve S, Kronke M: FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral spingomyelinase. Cell 86:937–947, 1996

    Google Scholar 

  72. Kreder D, Krut O, Adam-Klages S, Wiegmann K, Scherer G, Plitzt T, Jensen JM, Proksch E, Steinmann J, Pfeffer K, Kronke M: Impaired neutral spingomyelinase activation and cutaneous barrier repair in FAN-deficient mice. EMBO J 18:2472–2479, 1999

    Google Scholar 

  73. Brekke OL, Shalaby MR, Sundan A, Espevik T, Bjerve KS: Butylated hydroxyanisole specifically inhibits tumor necrosis factor-induced cytotoxicity and growth enhancement. Cytokine 4:269–280, 1992

    Google Scholar 

  74. Talley AK, Dewhurst S, Perry SW, Dollard SC, Gummuluru S, Fine SM, New D, Epstein LG, Gendelman HE, Gelbard HA: Tumor necrosis factor alpha-induced apoptosis in human neuronal cells: Protection by the antioxidant N-acetylcysteine and the genes bcl-2 and crmA. Mol Cell Biol 15:2359–2366, 1995

    Google Scholar 

  75. Xu Y, Bialik S, Jones BE, Iimuro Y, Kitsis RN, Srinivasan A, Brenner DA, Czaja MJ: NF-kappaB inactivation converts a hepatocyte cell line TNF-alpha response from proliferation to apoptosis. Am J Physiol 275:C1058-C1066, 1998

    Google Scholar 

  76. Giri DK, Aggarwal BB: Constitutive activation of NF-kappaB causes resistance to apoptosis in human cutaneous T cell lymphoma HuT-78 cells. Autocrine role of tumor necrosis factor and reactive oxygen intermediates. J Biol Chem 273:14008–14014, 1998

    Google Scholar 

  77. Shrivastava A, Aggarwal BB: Antioxidants differentially regulate activation of nuclear factor-κB (NF-κB), activator protein-1, c-Jun N-terminal kinases (JNK), and apoptosis induced by tumor necrosis factor. Antiox Redox Signal 1:181–191, 1999

    Google Scholar 

  78. Liu B, Andrieu-Abadie N, Levade T, Zhang P, Obeid LM, Hannun YA: Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death. J Biol Chem 273:11313–11320, 1998

    Google Scholar 

  79. Schulze-Osthoff K, Beyaert R, Vandevoorde V, Haegeman G, Fiers W: Depletion of the mitochondrial electron transport abrogates the cytotoxic and gene-inductive effects of TNF. EMBO J 12:3095–3104, 1993

    Google Scholar 

  80. Goossens V, Grooten J, De Vos K, Fiers W: Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity. Proc Natl Acad Sci USA 92:8115–8119, 1995

    Google Scholar 

  81. Higuchi M, Aggarwal BB, Yeh ET: Activation of CPP32-like protease in tumor necrosis factor-induced apoptosis is dependent on mitochondrial function. J Clin Invest 99:1751–1758, 1997

    Google Scholar 

  82. Li JJ, Oberley LW: Overexpression of manganese-containing superoxide dismutase confers resistance to the cytotoxicity of tumor necrosis factor alpha and/or hyperthermia. Cancer Res 57:1991–1998, 1997

    Google Scholar 

  83. Higuchi M, Proske RJ, Yeh ET: Inhibition of mitochondrial respiratory chain complex I by TNF results in cytochrome c release, membrane permeability transition, and apoptosis. Oncogene 17:2515–2524, 1998

    Google Scholar 

  84. De Vos K, Goossens V, Boone E, Vercammen D, Vancompernolle K, Vandenabeele P, Haegeman G, Fiers W, Grooten J: The 55-kDa tumor necrosis factor receptor induces clustering of mitochondria through its membrane-proximal region. J Biol Chem 273:9673–9680, 1998

    Google Scholar 

  85. Bradham CA, Qian T, Streetz K, Trautwein C, Brenner DA, Lemasters JJ: The mitochondrial permeability transition is required for tumor necrosis factor alpha-mediated apoptosis and cytochrome c release. Mol Cell Biol 18:6353–6364, 1998

    Google Scholar 

  86. Rutka JT, Giblin JR, Berens ME, Enar B-S, Tokuda K, McCulloch JR, Rosenblum ML, Eessalu TE, Aggarwal BB, Bodell WJ: The effects of human recombinant tumor necrosis factor on glioma derived cell lines: Cellular proliferation, cytotoxicity, morphological and radioreceptor studies. Int J Cancer 41:573–582, 1988

    Google Scholar 

  87. Pastorino JG, Simbula G, Yamamoto K, Glascott PA Jr, Rothman RJ, Farber JL: The cytotoxicity of tumor necrosis factor depends on induction of the mitochondrial permeability transition. J Biol Chem 271:29792–29798, 1996

    Google Scholar 

  88. Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, Takagi M, Matsumoto K, Miyazone K, Gotoh Y: Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK-JNK and p38 signaling pathways. Science 275:90–94, 1997

    Google Scholar 

  89. Gotoh Y, Cooper JA: Reactive oxygen species and dimerisation-induced activation of apoptosis signal-regulating kinase 1 in tumor necrosis factor-alpha signal transduction. J Biol Chem 273:17477–17482, 1998

    Google Scholar 

  90. Voelkel-Johnson C, Entingh AJ, Wold WS, Gooding LR, Laster SM: Activation of intracellular proteases is an early event in TNF-induced apoptosis. J Immunol 154:1707–1716, 1995

    Google Scholar 

  91. Higuchi M, Singh S, Chan H, Aggarwal BB: Protease inhibitors differentially regulate tumor necrosis factor-induced apoptosis, nuclear factor-kappa B activation, cytotoxicity, and differentiation. Blood 86:2248–2256, 1995

    Google Scholar 

  92. Van Molle W, Libert C, Fiers W, Brouckaert P: Alpha 1-acid glycoprotein and alpha 1-antitrypsin inhibit TNF-induced but not anti-Fas-induced apoptosis of hepatocytes in mice. J Immunol 159:3555–3564, 1997

    Google Scholar 

  93. Deiss LP, Galinka H, Berissi H, Cohen O, Kimchi A: Cathepsin D protease mediates programmed cell death induced by interfer-on-gamma, Fas/APO-1 and TNF-alpha. EMBO J 15:3861–3870, 1996

    Google Scholar 

  94. Basu A: The involvement of novel protein kinase C isozymes in influencing sensitivity of breast cancer MCF-7 cells to tumor necrosis factor-alpha. Mol Pharmacol 53:105–111, 1998

    Google Scholar 

  95. Mayne GC, Murray AW: Evidence that protein kinase Cepsilon mediates phorbol ester inhibition of calphostin C-and tumor necrosis factor-alpha-induced apoptosis in U937 histiocytic lymphoma cells. J Biol Chem 273:24115–24121, 1998

    Google Scholar 

  96. Yeung MC, Liu J, Lau AS: An essential role for the interferon-inducible, double-stranded RNA-activated protein kinase PKR in the tumor necrosis factor-induced apoptosis in U937 cells. Proc Natl Acad Sci USA 93:12451–12455, 1996

    Google Scholar 

  97. Roulston A, Reinhard C, Amiri P, Williams LT: Early activation of c-Jun N-terminal kinase and p38 kinase regulate cell survival in response to tumor necrosis factor alpha. J Biol Chem 273:10232–10239, 1998

    Google Scholar 

  98. Guo YL, Baysal K, Kang B, Yang LJ, Williamson JR: Correlation between sustained c-Jun N-terminal protein kinase activation and apoptosis induced by tumor necrosis factor-alpha in rat mesangial cells. J Biol Chem 273:4027–4034, 1998

    Google Scholar 

  99. Johannes FJ, Horn J, Link G, Haas E, Siemienski K, Wajant H, Pfizenmaier K: Protein kinase Cmu downregulation of tumor-necrosis-factor-induced apoptosis correlates with enhanced expression of nuclear-factor-kappaB-dependent protective genes. Eur J Biochem 257:47–54, 1998

    Google Scholar 

  100. Beyaert R, Vanhaesebroeck B, Declercq W, Van Lint J, Vandenabele P, Agostinis P, Vandenheede JR, Fiers W: Casein kinase-1 phosphorylates the p75 tumor necrosis factor receptor and negatively regulates tumor necrosis factor signaling for apoptosis. J Biol Chem 270:23293–23299, 1995

    Google Scholar 

  101. Wright SC, Zheng H, Zhong J, Torti FM, Larrick JW: Role of protein phosphorylation in TNF-induced apoptosis: Phosphatase inhibitors synergize with TNF to activate DNA fragmentation in normal as well as TNF-resistant U937 variants. J Cell Biochem 53:222–233, 1993

    Google Scholar 

  102. Totpal K, Agarwal S, Aggarwal BB: Phosphatase inhibitors modulate the growth-regulatory effects of human tumor necrosis factor on tumor and normal cells. Cancer Res 52:2557–2562, 1992

    Google Scholar 

  103. Perez M, Haschke B, Donato NJ: Differential expression and translocation of protein tyrosine phosphatase 1B-related proteins in ME-180 tumor cells expressing apoptotic sensitivity and resistance to tumor necrosis factor: Potential interaction with epidermal growth factor receptor. Oncogene 18:967–978, 1999

    Google Scholar 

  104. Aggarwal BB, Totpal K, Ali-Osman F, Budde R, Pocsik E: pp60V-src kinase overexpression leads to the cellular resistance to the antiproliferative effects of tumor necrosis factor. FEBS Lett 345:219–224, 1994

    Google Scholar 

  105. Aggarwal BB, Pocsik E, Totpal K, Ali-Osman F: Suppression of antiproliferative effects of tumor necrosis factor by transfection of cells with human platelet-derived growth factor B/c-sis gene. FEBS Lett 357:1–6, 1995

    Google Scholar 

  106. Sugarman BJ, Lewis GD, Eessalu TE, Aggarwal BB, Shepard HM: Effects of growth factors on the antiproliferative activity of tumor necrosis factors. Cancer Res 47:780–786, 1987

    Google Scholar 

  107. Aggarwal BB, Pocsik E, Ali-Osman F, Totpal K: Transfection of cells with transforming growth factor-α leads to cellular resistance to the antiprolifeative effects of tumor necrosis factor. FEBS Lett 354:12–16, 1994

    Google Scholar 

  108. Aggarwal BB, Pocsik E, Totpal K: Transfection of cells with basic fibroblast growth factor and Kaposi fibroblast growth factor genes induce resistance to and receptor modulation of tumor necrosis factor. FEBS Lett 372:44–48, 1995

    Google Scholar 

  109. Hudziak RM, Lewis GD, Eessalu TE, Aggarwal BB, Ullrich A, Shepard HM: Amplified expression of the HER2/ERBB2 oncogene induces resistance to tumor necrosis factor-α in NIH 3T3 cells. Proc Natl Acad Sci USA 85:5102–5106, 1988

    Google Scholar 

  110. Hsu H, Xiong J, Goeddel DV: The TNF receptor 1-associated protein TRADD signals cell death and NFkB activation. Cell 81:495–504, 1995

    Google Scholar 

  111. Hsu H, Shu HB, Pan MG, Goeddel DV: TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84:299–308, 1996

    Google Scholar 

  112. Darnay BG, Singh S, Chaturvedi MM, Aggarwal BB: The p60 tumor necrosis factor (TNF) receptor-associated kinase (TRAK) binds residues 344–397 within the cytoplasmic domain involved in TNF signaling. J Biol Chem 270:14867–14870, 1995

    Google Scholar 

  113. Liou ML, Liou HC: The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis. J Biol Chem 274:10145–10153, 1999

    Google Scholar 

  114. Castellino AM, Parker GJ, Boronenkov IV, Anderson RA, Chao MV: A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase. J Biol Chem 272:5861–5870, 1997

    Google Scholar 

  115. Schievella AR, Chen JH, Graham JR, Lin LL: MADD, a novel death domain protein that interacts with the type 1 tumor necrosis factor receptor and activates mitogen-activated protein kinase. J Biol Chem 272:12069–12075, 1997

    Google Scholar 

  116. Song HY, Dunbar JD, Zhang YX, Guo D, Donner DB: Identification of a protein with homology to hsp 90 that binds the type 1 tumor necrosis factor receptor. J Biol Chem 270:3574–3581, 1995

    Google Scholar 

  117. Dunbar JD, Song HY, Guo D, Wu LW, Donner DB: Two-hybrid cloning of a gene encoding TNF receptor-associated protein 2, a protein that interacts with the intracellular domain of the type 1 TNF receptor: Identity with subunit 2 of the 26S protease. J Immunol 158:4252–4259, 1997

    Google Scholar 

  118. Gu C, Castellino A, Chan JY, Chao MV: BRE: A modulator of TNF-alpha action. FASEB J 12:1101–1108, 1998

    Google Scholar 

  119. Wallach D, Varfolomeev EE, Malinin NL, Goltsev YV, Kovalenko AV, Boldin MP: Tumor necrosis factor receptor and Fas signaling mechanisms. Annu Rev Immunol 17:331–367, 1999

    Google Scholar 

  120. Cheng G, Baltimore D: TANK, a co-inducer with TRAF2 of TNF-and CD 40L-mediated NF-kappaB activation. Genes Dev 10:963–973, 1996

    Google Scholar 

  121. Jiang Y, Woronicz JD, Liu W, Goeddel DV: Prevention of constitutive TNF receptor 1 signaling by silencer of death domains. Science 283:543–546, 1999

    Google Scholar 

  122. Zhu N, Khoshnan A, Schneider R, Matsumoto M, Dennert G, Ware C, Lai MM: Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis. J Virol 72:3691–3697, 1998

    Google Scholar 

  123. Hildt E, Oess S: Identification of Grb2 as a novel binding partner of tumor necrosis factor (TNF) receptor I. J Exp Med 189:1707–1714, 1999

    Google Scholar 

  124. Rothe M, Sarma V, Dixit VM, Goeddel DV: TRAF2-mediated activation of NF-kB by TNF receptor 2 and CD40. Science 269:1424–1427, 1995

    Google Scholar 

  125. Yeh WC, Shahinian A, Speiser D, Kraunus J, Billia F, Wakeham A, de la Pompa J, Ferrick D, Hum B, Iscove N, Ohashi P, Rothe M, Goeddel DV, Mak TW: Early lethality, functional NFkB activation and increased sensitivity to TNF induced cell death in TRAF2-deficient mice. Immunity 7:715–725, 1997

    Google Scholar 

  126. Stanger BZ, Leder P, Lee TH, Kim E, Seed B: RIP: A novel protein containing a death domain that interacts with Fas/APO1 (CD95) in yeast and causes cell death. Cell 81:513–523, 1995

    Google Scholar 

  127. Kelliher MA, Grimm S, Ishida Y, Kuo F, Stanger BZ, Leder P: The death domain kinase RIP mediates the TNF-induced NF-kappa B signal. Immunity 8:297–303, 1998

    Google Scholar 

  128. Ling L, Cao Z, Goeddel DV: NFkB-inducing kinase activates IKK-a by phosphorylation of Ser-176. Proc Natl Acad Sci USA 95:3792–3797, 1998

    Google Scholar 

  129. Ferran C, Stroka DM, Badrichani AZ, Cooper JT, Wrighton CJ, Soares M, Grey ST, Bach FH: A20 inhibits NF-kappaB activation in endothelial cells without sensitizing to tumor necrosis factor-mediated apoptosis. Blood 91:2249–2258, 1998

    Google Scholar 

  130. Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM: FADD, a novel death domain containing protein interacts with the death domain of Fas and initiates apoptosis. Cell 81:505–512, 1995

    Google Scholar 

  131. Boldin MP, Goncharov TM, Goltsev YV, Wallach D: Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO1 and TNF receptor-induced cell death. Cell 85:803–817, 1996

    Google Scholar 

  132. Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter M, Dixit VM: FLICE, a novel FADD-homologous ICE-CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death inducing signaling complex. Cell 85:817–827, 1996

    Google Scholar 

  133. Darnay BG, Singh S, Aggarwal BB: The p80 TNF receptor-associated kinase (p80 TRAK) associates with residues 354–397 of the p80 cytoplasmic domain: Similarity to casein kinase. FEBS Lett 406:101–105, 1997

    Google Scholar 

  134. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S: A caspase activated DNase that degrades DNA during apoptosis and its inhibitor ICAD. Nature 391:43–50, 1998

    Google Scholar 

  135. Wang CY, Cusack JC Jr, Liu R, Baldwin AS Jr: Control of inducible chemoresistance: Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kB. Nature Med 5:412–417, 1999

    Google Scholar 

  136. Natoli G, Costanzo A, Guido F, Moretti F, Bernardo A, Burgio VL, Agresti C, Levrero M: Nuclear factor kB independent cytoprotective pathways originating at tumor necrosis factor receptor-associated factor 2. J Biol Chem 273:31262–31272, 1998

    Google Scholar 

  137. Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV: TRAF 6 is a signal transducer for interleukin-1. Nature 383:443–446, 1996

    Google Scholar 

  138. Goeddel DV: Cytokine meeting, Report, 1999

  139. Zhang J, Cado D, Chen A, Kabra NH, Winoto A: Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/MORT1. Nature 392:296–300, 1998

    Google Scholar 

  140. Yeh W, de la Pompa JL, McCurrach ME, Shu H, Elia AJ, Shahinian A, Ng M, Wakeham A, Khoo W, Mitchell K, El-Deiry WS, Lowe SW, Goeddel DV, Mak TW: FADD: Essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science 279:1954–1958, 1998

    Google Scholar 

  141. Varfolomeev EE, Schuchmann M, Luria V, Chiannikulchai N, Beckmann JS, Mett IL, Rebrikov D, Brodianski VM, Kemper OC, Kollet O, Lapidot T, Soffer D, Sobe T, Avraham KB, Goncharov T, Holtmann H, Lonai P, Wallach D: Targeted disruption of the mouse caspase-8 gene ablates cell death induction by the TNF receptors, Fas/Apol and DR3 and is lethal prenatally. Immunity 9:267–276, 1998

    Google Scholar 

  142. Hu Y, Baud V, Delhase M, Zhang P, Deerinck T, Ellisman M, Johnson R, Karin M: Abnormal morphogenesis but intact IKK activation in mice lacking the IKK a subunit of the IkB kinase. Science 284:316–320, 1999

    Google Scholar 

  143. Li Z-W, Chu W, Hu Y, Delhase M, Deerinck T, Ellisman M, Johnson R, Karin M: The IKK b subunit of IkB kinase (IKK) is essential for Nuclear Factor kB activation and prevention of apoptosis. J Exp Med 189:1839–1845, 1999

    Google Scholar 

  144. Kuida K, Zheng TS, Na S, Kuan C, Yang D, Karasuyama H, Rakic P, Flavell RA: Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384:368–372, 1996

    Google Scholar 

  145. Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS, Elia A, de la Pompa JL, Kagi D, Khoo W, Potter J, Yoshida R, Kaufman SA, Lowe SW, Penninger JM, Mak TW: Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94:339–352, 1998

    Google Scholar 

  146. Kuida K, Haydar TF, Kuan CY, Gu Y, Taya C, Karasuyama H, Su MS, Rakic P, Flavell RA: Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94:325–337, 1998

    Google Scholar 

  147. Yoshida H, Kong YY, Yoshida R, Elia AJ, Hakem A, Hakem R, Penninger JM, Mak TW: Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Cell 94:739–750, 1998

    Google Scholar 

  148. Lee SY, Reichlin A, Santana A, Sokol KA, Nussenzweig MC, Choi Y: TRAF2 is essential for JNK but not NFkB activation and regulates lymphocyte proliferation and survival. Immunity 7:703–713, 1997

    Google Scholar 

  149. Sun X, Lee J, Navas T, Baldwin DT, Stewart TA, Dixit VM: RIP 3, a novel apoptosis-inducing kinase. J Biol Chem 274:16871–16875, 1999

    Google Scholar 

  150. Schwandner R, Wiegmann K, Bernardo K, Kreder D, Kronke M: TNF receptor death domain-associated proteins TRADD and FADD signal activation of acid spingomyelinase. J Biol Chem 273:5916–5922, 1998

    Google Scholar 

  151. Weigmann K, Schwandner R, Krut O, Yeh WC, Mak TW, Kronke M: Requirement of FADD for tumor necrosis factor-induced activation of acid spingomyelinase. J Biol Chem 274:5267–5270, 1999

    Google Scholar 

  152. Wolf BB, Green DR: Suicidal tendencies: Apoptotic cell death by caspase family proteinases. J Biol Chem 274:20049–20052, 1999

    Google Scholar 

  153. Bossy-Wetzel E, Green DR: Caspases induce cytochrome c release from mitochondria by activating cytosolic factors. J Biol Chem 274:17484–17490, 1999

    Google Scholar 

  154. Sun XM, MacFarlane M, Zhuang J, Wolf BB, Green DR, Cohen GM: Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J Biol Chem 274:5053–5060, 1999

    Google Scholar 

  155. Rathmell JC, Thompson CB: The central effectors of cell death in the immune system. Annu Rev Immunol 17:781–828, 1999

    Google Scholar 

  156. Janicke RU, Sprengart ML, Wati MR, Porter AG: Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 273:9357–9360, 1998

    Google Scholar 

  157. Qin H, Srinivasulu SM, Wu G, Fernandes-Alnemri T, Alnemri ES, Shi Y: Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1. Nature 399:549–557, 1999

    Google Scholar 

  158. Beg AA, Baltimore D: An essential role for NF-kB in preventing TNF-alpha-induced cell death. Science 274:782–784, 1996

    Google Scholar 

  159. van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM: Suppression of TNF-alpha-induced apoptosis by NF-kB. Science 274:787–789, 1996

    Google Scholar 

  160. Wang CY, Mayo MW, Baldwin AS Jr: TNF-and cancer therapy-induced apoptosis: Potentiation by inhibition of NF-kappaB. Science 274:784–787, 1996

    Google Scholar 

  161. Bakker TR, Reed D, Renno T, Jongeneel CV: Efficient adenoviral transfer of NF-kappaB inhibitor sensitizes melanoma to tumor necrosis factor-mediated apoptosis. Int J Cancer 80:320–323, 1999

    Google Scholar 

  162. Cai Z, Capoulade C, Moyret-Lalle C, Amor-Gueret M, Feunteun J, Larsen AK, Paillerets BB, Chouaib S: Resistance of MCF7 human breast carcinoma cells to TNF-induced cell death is associated with loss of p53 function. Oncogene 15:2817–2826, 1997

    Google Scholar 

  163. Doi TS, Marino MW, Takahashi T, Yoshida T, Sakakura T, Old LJ, Obata Y: Absence of tumor necrosis factor rescues RelAdeficient mice from embryonic lethality. Proc Natl Acad Sci USA 96:2994–2999, 1999

    Google Scholar 

  164. Yin D, Kondo S, Barnett GH, Morimura T, Takeuchi J: Tumor necrosis factor-alpha induces p53-dependent apoptosis in rat glioma cells. Neurosurgery 37:758–762, 1995

    Google Scholar 

  165. Sheikh MS, Burns TF, Huang Y, Wu GS, Amundson S, Brooks KS, Fornace AJ Jr, El-Deiry WS: p53-dependent and-independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor alpha. Cancer Res 58:1593–1598, 1998

    Google Scholar 

  166. Yeung MC, Lau AS: Tumor suppressor p53 as a component of the tumor necrosis factor-induced, protein kinase PKR-mediated apoptotic pathway in human promonocytic U937 cells. J Biol Chem 273:25198–25202, 1998

    Google Scholar 

  167. Donato NJ, Perez M: Tumor necrosis factor-induced apoptosis stimulates p53 accumulation and p21WAFI proteolysis in ME-180 cells. J Biol Chem 273:5067–5072, 1998

    Google Scholar 

  168. Tan X, Martin SJ, Green DR, Wang JYJ: Degradation of retinoblastoma protein in tumor necrosis factor-and CD95-induced cell death. J Biol Chem 272:9613–9616, 1997

    Google Scholar 

  169. Janicke RU, Lin XY, Lee FH, Porter AG: Cyclin D3 sensitizes tumor cells to tumor necrosis factor-induced, c-Myc-dependent apoptosis. Mol Cell Biol 16:5245–5253, 1996

    Google Scholar 

  170. Trent JC, 2nd, McConkey DJ, Loughlin SM, Harbison MT, Fernandez A, Ananthaswamy HN: Ras signaling in tumor necrosis factor-induced apoptosis. EMBO J 15:4497–4505, 1996

    Google Scholar 

  171. Singh N, Sun Y, Nakamura K, Smith MR, Colburn NH: C-JUN/AP-1 as possible mediators of tumor necrosis factor-alpha-induced apoptotic response in mouse JB6 tumor cells. Oncol Res 7:353–362, 1995

    Google Scholar 

  172. Kim YM, de Vera ME, Watkins SC, Billiar TR: Nitric oxide protects cultured rat hepatocytes from tumor necrosis factor-alpha-induced apoptosis by inducing heat shock protein 70 expression. J Biol Chem 272:1402–1411, 1997

    Google Scholar 

  173. Heneka MT, Loschmann PA, Gleichmann M, Weller M, Schulz JB, Wullner U, Klockgether T: Induction of nitric oxide synthase and nitric oxide-mediated apoptosis in neuronal PC12 cells after stimulation with tumor necrosis factor-alpha/lipopolysaccharide. J Neurochem 71:88–94, 1998

    Google Scholar 

  174. Kumar A, Commane M, Flickinger TW, Horvath CM, Stark GR: Defective TNF-alpha-induced apoptosis in STAT1-null cells due to low constitutive levels of caspases [see Comments]. Science 278:1630–1632, 1997

    Google Scholar 

  175. Denecker G, Vandenabeele P, Grooten J, Penning LC, Declercq W, Beyaert R, Buurman WA, Fiers W: Differential role of calcium in tumour necrosis factor-mediated apoptosis and secretion of granulocyte-macrophage colony-stimulating factor in a T cell hybridoma. Cytokine 9:631–638, 1997

    Google Scholar 

  176. Kissil JL, Cohen O, Raveh T, Kimchi A: Structure-function analysis of an evolutionary conserved protein, DAP3, which mediates TNF-alpha-and Fas-induced cell death. EMBO J 18:353–362, 1999

    Google Scholar 

  177. Testa U, Grignani F, Samoggia P, Zanetti C, Riccioni R, Coco FL, Diverio D, Felli N, Passerini CG, Grell M, Pelicci PG, Peschle C: The PML/RARalpha fusion protein inhibits tumor necrosis factor-alpha-induced apoptosis in U937 cells and acute promyelocytic leukemia blasts. J Clin Invest 101:2278–2289, 1998

    Google Scholar 

  178. Klefstrom J, Arighi E, Littlewood T, Jaattela M, Saksela E, Evan GI, Alitalo K: Induction of TNF sensitive cellular phenotype by c-Myc involves p53 and impaired NF-kB activation. EMBO J 16:7382–7392, 1997

    Google Scholar 

  179. Soengas MS, Alarcon RM, Yoshida H, Giaccia AJ, Hakem R, Mak TW, Lowe SW: Apaf-1 and Caspase-9 in p53-dependent apoptosis and tumor inhibition. Science 284:156–159, 1999

    Google Scholar 

  180. Bennett M, Macdonald K, Chan S-W, Luzio JP, Simari R, Weissberg P: Cell surface traffiking of Fas: A rapid mechanism of p53-mediated apoptosis [see Comments]. Science 282:290–293, 1998

    Google Scholar 

  181. Aggarwal BB, Eessalu TE: Induction of receptors for tumor necrosis factor-alpha by interferons is not a major mechanism for their synergistic cytotoxic response. J Biol Chem 262:10000–10007, 1987

    Google Scholar 

  182. Andrews T, Zhang P, Bhat NR: TNFalpha potentiates IFN-gamma-induced cell death in oligodendrocyte progenitors. J Neurosci Res 54:574–583, 1998

    Google Scholar 

  183. Delic J, Masdehors P, Omura S, Cosset JM, Dumont J, Binet JL, Magdelenat H: The proteasome inhibitor lactacystin induces apoptosis and sensitizes chemo-and radioresistant human chronic lymphocytic leukaemia lymphocytes to TNF-alpha-initiated apoptosis. Br J Cancer 77:1103–1107, 1998

    Google Scholar 

  184. Deptala A, Halicka HD, Ardelt B, Ardelt W, Mikulski SM, Shogen K, Darzynkiewicz Z: Potentiation of tumor necrosis factor induced apoptosis by onconase. Int J Oncol 13:11–16, 1998

    Google Scholar 

  185. Penning LC, Schipper RG, Vercammen D, Verhofstad AA, Denecker T, Beyaert R, Vandenabeele P: Sensitization of tnf-induced apoptosis with polyamine synthesis inhibitors in different human and murine tumour cell lines. Cytokine 10:423–431, 1998

    Google Scholar 

  186. Galea-Lauri J, Richardson AJ, Latchman DS, Katz DR: Increased heat shock protein 90 (hsp90) expression leads to increased apoptosis in the monoblastoid cell line U937 following induction with TNF-alpha and cycloheximide: A possible role in immunopathology. J Immunol 157:4109–4118, 1996

    Google Scholar 

  187. Su F, Schneider RJ: Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor necrosis factor alpha. Proc Natl Acad Sci USA 94:8744–8749, 1997

    Google Scholar 

  188. Rayet B, Lopez-Guerrero JA, Rommelaere J, Dinsart C: Induction of programmed cell death by parvovirus H-1 in U937 cells: Connection with the tumor necrosis factor alpha signalling pathway. J Virol 72:8893–8903, 1998

    Google Scholar 

  189. Krajcsi P, Dimitrov T, Hermiston TW, Tollefson AE, Ranheim TS, Vande Pol SB, Stephenson AH, Wold WS: The adenovirus E3–14.7K protein and the E3–10.4K/14.5K complex of proteins, which independently inhibit tumor necrosis factor (TNF)-induced apoptosis, also independently inhibit TNF-induced release of arachidonic acid. J Virol 70:4904–4913, 1996

    Google Scholar 

  190. Datta R, Kojima H, Banach D, Bump NJ, Talanian RV, Alnemri ES, Weichselbaum RR, Wong WW, Kufe DW: Activation of a CrmA-insensitive, p35-sensitive pathway in ionizing radiation-induced apoptosis. J Biol Chem 272:1965–1969, 1997

    Google Scholar 

  191. Bergqvist A, Soderbarg K, Magnusson G: Altered susceptibility to tumor necrosis factor alpha-induced apoptosis of mouse cells expressing polyomavirus middle and small T antigens. J Virol 71:276–283, 1997

    Google Scholar 

  192. Kawanishi M: Epstein-Barr virus BHRF1 protein protects intestine 407 epithelial cells from apoptosis induced by tumor necrosis factor alpha and anti-Fas antibody. J Virol 71:3319–3322, 1997

    Google Scholar 

  193. Tewari M, Beidler DR, Dixit VM: CrmA-inhibitable cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein during Fas-and tumor necrosis factor-induced apoptosis. J Biol Chem 270:18738–18741, 1995

    Google Scholar 

  194. Miura M, Friedlander RM, Yuan J: Tumor necrosis factor-induced apoptosis is mediated by a CrmA-sensitive cell death pathway. Proc Natl Acad Sci USA 92:8318–8322, 1995

    Google Scholar 

  195. Gamard CJ, Dbaibo GS, Liu B, Obeid LM, Hannun YA: Selective involvement of ceramide in cytokine-induced apoptosis. Ceramide inhibits phorbol ester activation of nuclear factor kappaB. J Biol Chem 272:16474–16481, 1997

    Google Scholar 

  196. Schreiber M, Sedger L, McFadden G: Distinct domains of M-T2, the myxoma virus tumor necrosis factor (TNF) receptor homolog, mediate extracellular TNF binding and intracellular apoptosis inhibition. J Virol 1:2171–2181, 1997

    Google Scholar 

  197. Janicke RU, Porter AG, Kush A: A novel Arabidopsis thaliana protein protects tumor cells from tumor necrosis factor-induced apoptosis. Biochim Biophys Acta 1402:70–78, 1998

    Google Scholar 

  198. Kettle S, Alcami A, Khanna A, Ehret R, Jassoy C, Smith GL: Vaccinia virus serpin B13R (SPI-2) inhibits interleukin-1beta-converting enzyme and protects virus-infected cells from TNF-and Fas-mediated apoptosis, but does not prevent IL-1beta-induced fever. J Gen Virol 78:677–685, 1997

    Google Scholar 

  199. Ray RB, Meyer K, Steele R, Shrivastava A, Aggarwal BB, Ray R: Inhibition of tumor necrosis factor (TNF-alpha)-mediated apoptosis by hepatitis C virus core protein. J Biol Chem 273:2256–2259, 1998

    Google Scholar 

  200. Humphreys D, Hochgrebe TT, Easterbrook-Smith SB, Tenniswood MP, Wilson MR: Effects of clusterin overexpression on TNFalpha-and TGF beta-mediated death of L929 cells. Biochemistry 36:15233–15243, 1997

    Google Scholar 

  201. Spyridopoulos I, Principe N, Krasinski KL, Xu Sh, Kearney M, Magner M, Isner JM, Losordo DW: Restoration of E2F expression rescues vascular endothelial cells from tumor necrosis factor-alpha-induced apoptosis. Circulation 98:2883–2890, 1998

    Google Scholar 

  202. Kunstle G, Leist M, Uhlig S, Revesz L, Feifel R, MacKenzie A, Wendel A: ICE-protease inhibitors block murine liver injury and apoptosis caused by CD95 or by TNF-alpha. Immunol Lett 55:5–10, 1997

    Google Scholar 

  203. Marino MW, Dunbar JD, Wu LW, Ngaiza JR, Han HM, Guo D, Matsushita M, Nairn AC, Zhang Y, Kolesnick R, Jaffe EA, Donner DB: Inhibition of tumor necrosis factor signal transduction in endothelial cells by dimethylaminopurine. J Biol Chem 271:28624–28629, 1996

    Google Scholar 

  204. Habtemariam S: Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-alpha in L-929 tumor cells. J Nat Products 60:775–778, 1997

    Google Scholar 

  205. Halicka HD, Ardelt B, Li X, Melamed MM, Darzynkiewicz Z: 2-Deoxy-D-glucose enhances sensitivity of human histiocytic lymphoma U937 cells to apoptosis induced by tumor necrosis factor. Cancer Res 55:444–449, 1995

    Google Scholar 

  206. Murray J, Condliffe AM, Haslett C, Chilvers ER: Wortmannin enhances tumour necrosis factor alpha-stimulated neutrophil apoptosis. Biochem Soc Trans 24:80S, 1996

    Google Scholar 

  207. Koike T, Fehsel K, Zielasek J, Kolb H, Burkart V: Gangliosides protect from TNF alpha-induced apoptosis. Immunol Lett 35:207–212, 1993

    Google Scholar 

  208. Manna SK, Gad YP, Mukhopadhyay A, Aggarwal BB: Supression of tumor necrosis factor activated nuclear transcription factor kappa B, activator protein-1, c-Jun N-terminal kinase and apoptosis by beta-lapachone. Biochem Pharmacol 57:763–774, 1999

    Google Scholar 

  209. Kim YM, de Vera ME, Watkins SC, Billiar TR: Nitric oxide protects cultured rat hepatocytes from tumor necrosis factor-alpha-induced apoptosis by inducing heat shock protein 70 expression. J Biol Chem 272:1402–1411, 1997

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bharat B. Aggarwal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rath, P.C., Aggarwal, B.B. TNF-Induced Signaling in Apoptosis. J Clin Immunol 19, 350–364 (1999). https://doi.org/10.1023/A:1020546615229

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020546615229

Navigation