Death receptors and their ligands

  • Jürgen Holtz
  • Dorothea Darmer
Part of the Basic Science for the Cardiologist book series (BASC, volume 5)


The identification and description of an intrinsic program of regulated cellular suicide or apoptosis was originally obtained from morphological analyses in developmental biology (76, 77). This program exists in all multicellular organisms, and genetic analyses in the nematode Caenorhabditis elegans identified three ced-genes (for C. elegans death) as basal, highly conserved components of this program, see (39, 57). In mammals, several structural and functional homologs of these ced-encoded proteins are involved in the apoptosis regulating complex formation at the outer mitochondrial membrane (Fig. 1), the apoptosome (56, 124), such as Apaf-1 (for “apoptosis protease activating factor”) or proteins of the Bcl-2 family (see chapter I.2.2). Another important discovery from C. elegans genetics was the identification of interleukin-lß-converting enzyme (ICE or caspase-1) as a functional homolog of the ced-3 gene product. This discovery triggered the identification of a whole cascade of caspases (for “cysteine-containing aspartic acid proteases”, see chapter I.3.1). This cascade is involved in the execution phase of apoptosis (164), and one source for activating the cascade is the mitochondrial apoptosome (Fig. 1).


Tumor Necrosis Factor Death Receptor Tumor Necrosis Factor Receptor Death Domain Trail Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adam, D., K. Wiegman, S. Adam-Klages, A. Ruff, and M. Krönke. A novel cytoplasmic domain of the p55 TNF receptor initiates the neutral sphingomyelinase pathway. J Biol Chem 271: 14617–14622, 1996.PubMedGoogle Scholar
  2. 2.
    Adam-Klages, S., D. Adam, K. Wiegmann, S. Struve, W. Kolanus, J. Schneider-Mergener, and M. Kronke. Fan, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase. Cell 86: 937–947, 1996.PubMedGoogle Scholar
  3. 3.
    Aderka, D., H. Engelmann, Y. Maor, C. Brakebusch, and D. Wallach. Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med 175: 323–329, 1992.PubMedGoogle Scholar
  4. 4.
    Amarante-Mendes, G. P., A. J. McGahon, W. K. Nishioka, D. E. Afar, O. N. Witte, and D. R. Green. Bcl-2-independent Bcr-Abl-mediated resistance to apoptosis: protection is correlated with upregulationofBcl-xL. Oncogene 16: 1383–1390, 1998.PubMedGoogle Scholar
  5. 5.
    Anderson, D. M., E. Maraskovsky, W. L. Billingsley, W. C. Dougall, M. E. Tometsko, E. R. Roux, M. C. Teepe, R. F. DuBose, D. Cosman, and L. Galibert. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390: 175–179, 1997.PubMedGoogle Scholar
  6. 6.
    Ashkenazi, A., and V. M. Dixit. Death receptors: signaling and modulation, Science 281: 1305–1308, 1998.PubMedGoogle Scholar
  7. 7.
    Baeuerle, P. A., and D. Baltimore. NF-kB: ten years after. Cell 87: 13–21, 1996.PubMedGoogle Scholar
  8. 8.
    Barrett, G. L., and A. Georgiu. The low-affinity nerve growth factor receptor p75NGFR mediates death of PC12 cells after nerve growth factor withdrawal. J Neurosci Res 45: 117–128, 1996.PubMedGoogle Scholar
  9. 9.
    Battling, B., H. Milting, H. Schumann, A. El-Banayosy, M. Koerner, R. Koerfer, D. Darmer, J. Holtz, and H. R. Zerkowski. Improved myocardial expression of anti-apoptotic genes under support by ventricular assist devices (VAD) in terminal heart failure (abstr). Circulation 98(supll): 1–200, 1998.Google Scholar
  10. 10.
    Becker, K., P. Schneider, K. Hofmann, C. Mattmann, and J. Tschopp. Interaction of Fas (Apo-1/CD95) with proteins implicated in the ubiquitination pathway. FEBS Lett 412: 102–106, 1997.PubMedGoogle Scholar
  11. 11.
    Beg, A. A., and D. Baltimore. An essential role for NF-KB in preventing TNF-α-induced cell death. Science 274: 782–784, 1996.PubMedGoogle Scholar
  12. 12.
    Beutler, B., I. W. Milsark, and A. Cerami. Cachectin/tumor necrosis factor: production, distribution and metabolic fate in vivo. J Immunol 135: 3972–3977, 1985.PubMedGoogle Scholar
  13. 13.
    Bigda, J., I. Beletsky, C. Brakebusch, Y. Vasfolomeev, H, Engelmann, J. Bigda, H. Holtmann, and D. Wallach. Dual role of the p75 tumor necrosis factor (TNF) receptor in TNF cytotoxicity. J Exp Med 180: 445–460, 1994.PubMedGoogle Scholar
  14. 14.
    Black, R. A., C. T. Rauch, C. J. Kozlosky, J. L. Peschon, J. L. Slack, M. F. Wolfson, B. J. Castner, K. L. Stocking, P. Reddy, S. Srinivasan, N. Nelson, N, Boiani, K. A. Schooley, M. Gerhart, R. Davis, J. N. Fitzner, R. S. Johnson, R, J. Paxton, C. J. March, and D. P. Cerretti. A metalloproteinase disintegrin that releases tumor-necrosis factor-α from cells. Nature 385: 729–733, 1997.PubMedGoogle Scholar
  15. 15.
    Bodmer, J. L., K. Burns, P. Schneider, K. Hofmann, V. Steiner, M. Thome, T. Bornand, M. Hahne, M. Schroeter, K. Becker, A. Wilson, L. E. French, J. L. Browning, H. R. MacDonald, and J. Tschopp. TRAMP, a novel apoptosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas (APO-1/CD95). Immunity 6: 79–88, 1997.PubMedGoogle Scholar
  16. 16.
    Bozkurt, B., S. B. Kribbs, F. J. Clubb, L. H. Michael, V. V. Didenko, P. J. Hornsby, Y. Seta, H. Oral, F. G. Spinale, and D. L. Mann. Pathophysiologically relevant concentrations of tumor necrosis factor-α promote progressive left ventricular dysfunction and remodeling in rats. Circulation 97: 1382–1391, 1998.PubMedGoogle Scholar
  17. 17.
    Bradley, J. R., D. R. Johnson, and J. S. Pober. Four different classes of inhibitors of receptor-mediated endocytosis decrease tumor necrosis factor-induced gene expression in human endothelial cells. J Immunol 150: 5544–5555, 1993.PubMedGoogle Scholar
  18. 18.
    Brooks, P. C., and A. L. Et. Integrin αvβ3 antagonists promote tumor-regression by inducing apoptosis of angiogenic blood-vessels. Cell 79: 1157–1164, 1994.PubMedGoogle Scholar
  19. 19.
    Buckley, C. D., D. Pilling, N. V. Henriquez, G. Parsonage, K. Threlfall, D. Scheel-Toellner, D. L. Simmons, A. N. Akbar, J. M. Lord, and M. Salmon. RDG peptides induce apoptosis by direct caspase-3 activation. Nature 397: 534–539, 1999.PubMedGoogle Scholar
  20. 20.
    Burns, K., F. Martinon, C. Esslinger, H. Pahl, P. Schneider, J. L. Bodmer, F. Di Marco, L. French, and J. Tschopp. MyD88, an adapter protein involved in interleukin-1 signaling. J Biol Chem 273: 12203–12209, 1998.PubMedGoogle Scholar
  21. 21.
    Cascino, I., G. Papoff, R. De Maria, R. Testi, and G. Ruberti. Fas/Apo-1 (CD95) receptor lacking the intracytoplasmic signaling domain protects tumor cells from Fas-mediated apoptosis. J Immunol 156: 13–17, 1996.PubMedGoogle Scholar
  22. 22.
    Chang, H. Y., H. Nishitoh, X. Yang, H. Ichijo, and D. Baltimore. Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx. Science 281: 1860–1863, 1998.PubMedGoogle Scholar
  23. 23.
    Chaudhary, P. M., M. Eby, A. Jasmin, A. Bookwalker, J. Murray, and L. Hood. Death receptor 5, a new member of TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kB pathway. Immunity 7: 821–830, 1997.PubMedGoogle Scholar
  24. 24.
    Cheema, S. S., G. L. Barrett, and P. F. Bartlett. Reducing p75 nerve growth factor receptor levels using antisense oligonucleotides prevents the loss of axotomized sensory neurons in the dorsal root ganglia of newborn rats. J Neurosci Res 46: 239–245, 1996.PubMedGoogle Scholar
  25. 25.
    Chen, C. S., M. Mrksich, S. Huang, G. M. Whitesites, and D. E. Ingber. Geometric control of cell life and death. Science 276: 1425–1428, 1997.PubMedGoogle Scholar
  26. 26.
    Cheng, J., C. Liu, W. J. Koopman, and J. D. Mountz. Characterization of human Fas gene: exon/ intron organization and promoter region. J Immunol 154: 1239–1245, 1995.PubMedGoogle Scholar
  27. 27.
    Chicheportiche, Y., P. R. Bourdon, H. Xu, Y. M. Hsu, H. Scott, C. Hession, I. Garcia, and J. L. Browning. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J Biol Chem 272: 32401–32410, 1997.PubMedGoogle Scholar
  28. 28.
    Chinnaiyan, A. M., O. R. K, G. L. Yu, R. H. Lyons, M. Garg, D. R. Duan, L. Xing, R. Gentz, J. Ni, and V. M. Dixit. Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95. Science 274: 990–992, 1996.PubMedGoogle Scholar
  29. 29.
    Choi, K. B., F. Wong, J. M. Harlan, P. M. Chaudhary, L. Hood, and A. Karsan. Lipopolysaccharide mediates endothelial apoptosis by a FADD-dependent pathway. J Biol Chem 273: 20185–20188, 1998.PubMedGoogle Scholar
  30. 30.
    Chou, J. J., H. Matsuo, H. Duan, and G. Wagner. Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment. Cell 94: 171–180, 1998.PubMedGoogle Scholar
  31. 31.
    Chu, K. T., X. H. Niu, and L. T. Williams. A Fas-associated protein factor, FAF1, potentiates Fasmediated apoptosis. Proc Natl Acad Sci 92: 11894–11898, 1995.PubMedGoogle Scholar
  32. 32.
    Crowe, P. D., B. N. Walter, K. M. Mohler, C. Otten-Evans, R. A. Black, and C. F. Ware. A metalloprotease inhibitor blocks shedding of the 80-kD TNF receptor and TNF processing in T lymphocytes. J Exp Med 181: 1205–1208, 1995.PubMedGoogle Scholar
  33. 33.
    De Groote, D., G. E. Grau, I. Dehart, and P. Franchimont. Stabilization of functional tumor necrosis factor-a by its soluble TNF receptors. Eur Cytokine Netw 4: 359–362, 1993.PubMedGoogle Scholar
  34. 34.
    De Vos, K., V. Goossens, E. Boone, D. Vercammen, K. Vancompernolle, P. Vandenabeele, G. Haegeman, W. Fiers, and J. Grooten. The 55-kDa tumor necrosis factor receptor induces clustering of mitochondria through its membrane-proximal region. J Biol Chem 273: 9673–9680, 1998.PubMedGoogle Scholar
  35. 35.
    Decaudin, D., S. Geley, R. Hirsch, M. Castedo, P. Marchetti, A. Macho, R. Kofier, and G. Kroemer. Bcl-2 and Bcl-XL antagonize the mitochondrial dysfunction preceding nuclear apoptosis induced by chemotherapeutic agents. Cancer Res 57: 62–67, 1997.PubMedGoogle Scholar
  36. 36.
    Degli-Esposti, M. A., W. C. Dougall, P. J. Smolak, J. Waugh, C. A. Smith, and R. G. Goodwin. The novel receptor TRAIL-R4 induces NF-kB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity 7: 813–820, 1997.PubMedGoogle Scholar
  37. 37.
    Degli-Esposti, M. A., P. J. Smolak, H. Walczak, J. Waugh, C. P. Huang, R. F. DuBose, R. G. Goodwin, and C. A. Smith. Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med 186: 1165–1170, 1997.PubMedGoogle Scholar
  38. 38.
    Duan, H., and V. M. Dixit. Raidd is a new ‘death’ adapter molecule. Nature 385: 86–89, 1997.PubMedGoogle Scholar
  39. 39.
    Ellis, R. E., J. Yuan, and H. R. Horvitz. Mechanisms and functions of cell death. Annu Rev Cell Biol 7: 663–698, 1991.PubMedGoogle Scholar
  40. 40.
    Emery, J. G., P. McDonnell, M. B. Burke, K. C. Deen, S. Lyn, C. Silverman, E. Dul, E. R. Appelbaum, C. Eichman, R. DiPrinzio, R. A. Dodds, I. E. James, M. Rosenberg, J. C. Lee, and P. R. Young. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273: 14363–14367, 1998.PubMedGoogle Scholar
  41. 41.
    Engelmann, H., D. Novick, and D. Wallach. Two tumor necrosis factor-binding proteins purified from human urine: evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors. J Biol Chem 1990: 1531–1536, 1990.Google Scholar
  42. 42.
    Felzen, B., M. Shilkrut, H. Less, I. Sarapov, G. Maor, R. Coleman, R. B. Robinson, G. Berke, and O. Binah. Fas (CD95/Apo-l)-mediated damage to ventricular myocytes induced by cytotoxic T lymphocytes from perforin-deficient mice: a major role for Inositol 1, 4, 5-Triphosphate. Circ Res 82: 438–450, 1998.PubMedGoogle Scholar
  43. 43.
    Frade, J. M., A. Rodrigez-Tebar, and Y. A. Barde. Induction of cell death by endogenous nerve growth factor through its p75 receptor. Nature 383: 166–168, 1996.PubMedGoogle Scholar
  44. 44.
    Frisch, S. M., and E. Ruoslahti. Integrins and anoikis. Curr Opin Cell Biol 9: 701–706, 1997.PubMedGoogle Scholar
  45. 45.
    Goltsev, Y. V., A. V. Kovalenko, E. Arnold, E. E. Varfolomeev, V. M. Brodianskii, and D. Wallach. CASH, a novel caspase homologue with death effector domains. J Biol Chem 272: 19641–19644, 1997.PubMedGoogle Scholar
  46. 46.
    Gong, L., T. Kamitani, K. Fujise, L. S. Caskey, and E. T. Yeh. Preferential interaction of sentrin with a ubiquitin-conjugating enzyme, Ubc9. J Biol Chem 272: 28198–28201, 1997.PubMedGoogle Scholar
  47. 47.
    Grell, M., E. Douni, H. Wajant, M. Löhden, M. Clauss, B. Baxeiner, S. Georgopoulos, W. Lesslauer, G. Kollias, K. Pfizenmaier, and P. Scheurich. 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.PubMedGoogle Scholar
  48. 48.
    Griffith, T. S., and D. H. Lynch. TRAIL: a molecule with multiple receptors and control mechanisms. Curr Opin Immunol 10: 559–563, 1998.PubMedGoogle Scholar
  49. 49.
    Gross, A., X. M. Yin, K. Wang, M. C. Wei, J. Jockel, C. Milliman, H. Erdjument-Bromage, P. Tempst, and S. J. Korsmeyer. Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-Rl/Fas death. J Biol Chem 274: 1156–1163, 1999.PubMedGoogle Scholar
  50. 50.
    Gruss, H. J. Molecular, structural, and biological characteristics of the tumor necrosis factor ligand superfamily. Ira J Clin Lab Res 26: 143–159, 1996.Google Scholar
  51. 51.
    Han, D. K. M., P. M. Chaudhary, M. E. Wright, C. Friedman, B. J. Trask, R. T. Riedel, D. G. Baskin, S. M. Schwartz, and L. Hood. MRIT, a novel death-effector domain-containing protein, interacts with caspases and Bcl-xL and initiates cell death. Proc Natl Acad Sci 94: 11333–11338, 1997.PubMedGoogle Scholar
  52. 52.
    Han, Z., K. Bhalla, P. Pantazis, E. A. Hendrickson, and J. H. Wyche. Cif (Cytochrome c effluxinducing factor) activity is regulated by Bcl-2 and caspase and correlates with the activation of Bid. Mol Cell Biol 19: 1381–1389, 1999.PubMedGoogle Scholar
  53. 53.
    Han, Z., G. Li, T. A. Bremner, T. S. Lange, G. Zhang, R. Jemmerson, J. H. Wyche, and E. A. Hendrickson. A cytosolic factor is required for mitochondria] cytochrome c efflux during apoptosis. Cell Death Diff 5: 469–479, 1998.Google Scholar
  54. 54.
    Hardimann, G., F. L. Rock, S. Balasubramanian, R. A. Kastelein, and J. F. Bazan. Molecular characterization and modular analysis of human MyD88. Oncogene 13: 2467–2475, 1996.Google Scholar
  55. 55.
    Häusler, P., G. Papoff, A. Eramo, K. Reif, C. D. A., and G. Ruberti. Protection of CD95-mediated apoptosis by activation of phosphatidylinositide 3-kinase and protein kinase B. Eur J Immunol 28: 57–69, 1998.PubMedGoogle Scholar
  56. 56.
    Hengartner, M. O. CED-4 is a stranger no more. Nature 388: 714–715, 1997.PubMedGoogle Scholar
  57. 57.
    Hengartner, M. O., and H. R. Horvitz. Programmed cell death in Caenorhabditis elegans. Curr Opin Genet Dev 4: 581–-, 1994.PubMedGoogle Scholar
  58. 58.
    Hennet, T., C. Richter, and E. Peterhans. Tumour necrosis factor-α induces Superoxide anion generation in mitochondria of L929 cells. Biochem J 289: 587–592, 1993.PubMedGoogle Scholar
  59. 59.
    Higuchi, M., R. J. Proske, and E. T. H. Yeh. Inhibition of mitochondria! respiration chain complex I by TNF results in cytochrome c release, membrane permeability transition, and apoptosis. Oncogene 17: 2515–2524, 1998.PubMedGoogle Scholar
  60. 60.
    Hofmann, K., P. Bucher, and J. Tschopp. The CARD domain: a new apoptotic signalling motif. Trends Biochem Sci 22: 155–156, 1997.PubMedGoogle Scholar
  61. 61.
    Hohmann, H. P., R. Remy, M. Brockhaus, and A. P. Van Loon. Two different cell types have different major receptors for human tumor necrosis factor (TNF alpha). J Biol Chem 264: 14927–14934, 1989.PubMedGoogle Scholar
  62. 62.
    Holmstrom, T. H., S. C. Chow, I. Elo, E. T. Coffey, S. Orrenius, L. Sistonen, and J. E. Eriksson. Suppression of Fas/APO-1-mediated apoptosis by mitogen-activated kinase signaling. J Immunol 160: 2626–2636, 1998.PubMedGoogle Scholar
  63. 63.
    Hu, S., C. Vincenz, J. Ni, R. Gentz, and V. M. Dixit. I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1-and CD-95-induced apoptosis. J Biol Chem 272: 17255–17257, 1997.PubMedGoogle Scholar
  64. 64.
    Inohara, N., L. del Peso, T. Koseki, S. Chen, and G. Núnez. RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. J Biol Chem 273: 12296–12300, 1998.PubMedGoogle Scholar
  65. 65.
    Inohara, N., T. Koseki, Y. Hu, S. Chen, and Núnez, G. CLARP, a death effector domain-containing protein interacts with caspase-8 and regulates apoptosis. Proc Nati Acad Sci 94: 10717–10722, 1997.Google Scholar
  66. 66.
    Irmler, M., M. Thome, M. Hahne, P. Schneider, K. Hofmann, V. Steiner, J. L. Bodmer, M. Schroeter, K. Burns, C. Mattmann, D. Rimoldi, L. E. French, and J. Tschopp. Inhibition of death receptor signals by cellular FLIP. Nature 388: 190–195, 1997.PubMedGoogle Scholar
  67. 67.
    Itoh, N., and S. Nagata. A novel protein domain required for apoptosis: mutational analysis of human Fas antigen. J Biol Chem 268: 10932–10937, 1993.PubMedGoogle Scholar
  68. 68.
    Itoh, N., S. Yonehara, A. Ishii, M. Yonehara, S. Mizushima, M. Sameshima, A. Hase, Y. Seto, and S. Nagata. The polypeptide encoded by the cDNA for human surface antigen Fas can mediate apoptosis. Cell 66: 233–243, 1991.PubMedGoogle Scholar
  69. 69.
    Jaattela, M., H. Mouritzen, F. Elling, and L. Bastholm. A20 zinc finger protein inhibits TNF and IL-1 signaling. J Immunol 156: 1166–1173, 1996.PubMedGoogle Scholar
  70. 70.
    Jaunin, F., K. Bums, J. Tschopp, T. E. Martin, and S. Fakan. Ultrastructural distribution of the death-domain-containing MyD88 protein in HeLa cells, Exp Cell Res 243: 67–75, 1998.PubMedGoogle Scholar
  71. 71.
    Jiang, Y., J. D. Woronicz, and D. V. Goeddel, Prevention of constitutive TNF receptor signaling by silencer of death domains. Science 283: 543–546, 1999.PubMedGoogle Scholar
  72. 72.
    Kagan, B. L., R. L. Baldwin, D. Munoz, and B. J., Wisnieski. Formation of ion-permeable channels by tumor necrosis factor-α. Science 257: 1427–1430, 1993.Google Scholar
  73. 73.
    Kamitani, T., K. Kito, H. P. Nguyen, H. F.-K. Wada, T., and E. T. Yeh. Identification of three sentrinization sites in PML. J Biol Chem 273: 26675–26682, 1998.PubMedGoogle Scholar
  74. 74.
    Kamitani, T., H. P. Nguyen, and E. T. Yeh. Preferential modification of nuclear proteins by a novel ubiquitin-like molecule. J Biol Chem 272: 14001–14004, 1997.PubMedGoogle Scholar
  75. 75.
    Kekelar, A., and C. B. Thompson. Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol 8: 324–330, 1998.Google Scholar
  76. 76.
    Kerr, J. F. R. Shrinkage necrosis: a distinct mode of cellular death. J Pathol 105: 13–20, 1971.PubMedGoogle Scholar
  77. 77.
    Kerr, J. F. R., A. H. Wyllie, and A. R. Currie. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26: 239–257, 1972.PubMedGoogle Scholar
  78. 78.
    Kiriakidou, M., D. A. Driscoll, J. M. Lopez-Guisa, and J. F. Strauss. Cloning and expression of primate Daxx cDNAs and mapping of the human gene to chromosome 6p21.3 in the MHC region. DNA Cell Biol 16: 1289–1298, 1997.PubMedGoogle Scholar
  79. 79.
    Kischkel, F. C., S. Hellbardt, I. Behrmann, M. Germer, M. Pawlita, P. H. Krammer, and M. E. Peter. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. Embo J 14: 5579–5588, 1995.PubMedGoogle Scholar
  80. 80.
    Kitson, J., T. Raven, Y. P. Jiang, D. V. Goeddel, K. M. Giles, K. T. Pun, C. J. Grinham, R. Brown, and S. N. Farrow. A death-domain-containing receptor that mediates apoptosis. Nature 384: 372–375, 1996.PubMedGoogle Scholar
  81. 81.
    Kolesnick, R. N., and M. Krönke. Regulation of ceramide production and apoptosis. Ann Rev Physiol 60: 643–665, 1998.Google Scholar
  82. 82.
    Kroemer, G., B. Dallaporta, and M. Resche-Rigon. The mitochondrial death/life regulator in apoptosis and necrosis. Ann Rev Physiol 60: 619–642, 1998.Google Scholar
  83. 83.
    Kroemer, G., N. Zamzami, and S. A. Susin. Mitochondrial control of apoptosis. Immunol Today 18: 44–51, 1997.PubMedGoogle Scholar
  84. 84.
    Krown, K. A., M. T. Page, C. Nguyen, D. Zechner, V. Gutierrez, K. L. Comstock, C. C. Glembotski, P. J. E. Quintana, and R. A. Sabbadini. Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes-Involvement of the sphingolipid signaling cascade in cardiac cell death. J Clin Invest 98: 2854–2865, 1996.PubMedGoogle Scholar
  85. 85.
    Kubota, T., C. F. McTieman, C. S. Frye, A. J. Demetris, and A. M. Feldman. Cardiac-specific overexpression of tumor necrosis factor-alpha causes lethal myocarditis in transgenic mice. J Card Fail 3: 117–24, 1997.PubMedGoogle Scholar
  86. 86.
    Kubota, T., C. F. McTiernan, C. S. Frye, S. E. Slawson, B. H. Lemster, A. P. Koretsky, A. J. Demetris, and A. M. Feldman. Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ Res 81: 627–35, 1997.PubMedGoogle Scholar
  87. 87.
    Kubota, T., M. Miyagishima, G. S. Bounutas, C. F. McTiernan, and A. M. Feldman. Overexpression of tumor necrosis factor-a activates the expression of multiple members of the apoptosis pathway in transgenic mice. Circulation 98: 1–462, 1998.Google Scholar
  88. 88.
    Lacey, D. L., E. Timms, H. L. Tan, M. J. Kelley, C. R. Dunstan, T. Burgess, R. Elliott, A. Colombero, G. Elliott, S. Sully, and A. L. Et, Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93: 165–176, 1998.PubMedGoogle Scholar
  89. 89.
    Ledgerwood, E. C., J. B. Prins, N. A. Bright, D. R. Johnson, K. Wolfreys, J. S. Pober, S. O’Rahily, and J. R. Bradley. Tumor necrosis factor is delivered to mitochondria where a tumor necrosis factor-binding protein is localized. Lab Invest 78: 1583–1589, 1998.PubMedGoogle Scholar
  90. 90.
    Lee, S. Y., S. Y. Lee, and Y. Choi. TRAF-interacting protein (TRIP): a novel component of the tumor necrosis factor receptor (TNFR)-and CD30-TRAF signaling complexes that inhibits TRAF2-mediated NF-kB activation. J Exp Med 185: 1275–1285, 1997.PubMedGoogle Scholar
  91. 91.
    Liang, H., and S. W. Fesik. Three-dimensional structures of proteins involved in programmed cell death. J Mol Biol 274: 291–302, 1997.PubMedGoogle Scholar
  92. 92.
    Liepinsh, E., L. L. Hag, G. Otting, and C. F. Ibanez. NMR structure of the death domain of the p75 neurotrophin receptor. EMBO J 16: 4999–5005, 1997.PubMedGoogle Scholar
  93. 93.
    Liu, C., J. Cheng, and J. D. Mountz. Differential expression of human Fas mRNA species upon peripheral blood mononuclear cell activation. Biochem J 310: 957–963, 1995.PubMedGoogle Scholar
  94. 94.
    Liu, Y., E. Cigola, W. Cheng, J. Kajastura, G. Olivetti, T. H. Hintze, and P. Anversa. Myocyte nuclear mitotic division and programmed myocyte cell death characterize the cardiac myopathy induced by rapid ventricular pacing in dogs. Lab Invest 73: 771–787, 1995.PubMedGoogle Scholar
  95. 95.
    Liu, Z.-G., H. Hsu, D. Goeddel, and M. Karin. Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kB activation prevents cell death. Cell 87: 565–576, 1996.PubMedGoogle Scholar
  96. 96.
    MacFarlane, M., M. Ahmad, S. M. Srinivasula, T. Fernandes-Alnemri, G. M. Cohen, and E. S. Alnemri. Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL. J BiolChem 272: 25417–25420, 1997.Google Scholar
  97. 97.
    Malinin, N. L., M. P. Boldin, A. V. Kovalenko, and D. Wallach. MAP3K-related kinase involved in NF-kB induction by TNF, CD95 and IL-1. Nature 385: 540–544, 1997.PubMedGoogle Scholar
  98. 98.
    Marsters, S. A., J. P. Sheridan, C. J. Donahue, R. M. Pitti, C. L. Gray, A. D. Goddard, K. D. Bauer, and A. Ashkenazi. Apo-3, a new member of the tumor necrosis factor receptor family, contains a death domain and activates apoptosis and NF-kB. Current Biol 6: 1669–1676, 1996.Google Scholar
  99. 99.
    Marsters, S. A., J. P. Sheridan, R. M. Pitti, J. Brush, A. Goddard, and A. Ashkenazi. Identification of a ligand for the death-domain-containing receptor Apo-3. Curr Biol 8: 525–528, 1998.PubMedGoogle Scholar
  100. 100.
    Marsters, S. T., J. P. Sheridan, R. M. Pitti, A. Huang, M. Skubatch, D. Baldwin, J. Yuan, A. Gurney, A. D. Goddard, P. Godowski, and A. Ashkenazi. A novel receptor for Apo-2L/TRAIL contains a truncated death domain. Curr Biol 7: 1003–1006, 1997.PubMedGoogle Scholar
  101. 101.
    Marzo, I., C. Brenner, N. Zamzami, S. A. Susin, G. Beutner, D. Brdiczka, R. Remy, Z.-H. Xie, J. C. Reed, and G. Kroemer. The permeability pore complex: A target for apoptosis regulation by caspases and Bcl-2-related proteins. J Exp Med 187: 1261–1271, 1998.PubMedGoogle Scholar
  102. 102.
    Marzo, I., S. A. Susin, P. X. Petit, and L. Ravagnan. Caspases disrupt mitochondrial membrane barrier function. FEBS Lett 427: 198–202, 1998.PubMedGoogle Scholar
  103. 103.
    Meakin, S. O., and E. M. Shooter. The nerve growth factor family of receptors. Trends Neurosci 15: 323–331, 1992.PubMedGoogle Scholar
  104. 104.
    Medetna, J. P., C. Scaffidi, F. C. Hischkel, A. Shevchenko, M. Mann, P. H. Krammer, and M. E. Peter. FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). Embo J 16: 2794–2804, 1997.Google Scholar
  105. 105.
    Meredith, J. E., and M. A. Schwartz. Integrins, adhesion and apoptosis. Trends Cell Biol 7: 146–150, 1997.Google Scholar
  106. 106.
    Mohler, K. M., D. S. Torrance, C. A. Smith, R. G. Goodwin, K. E. Stremler, V. F. Fung, H. Madami, and M. B. Widmer. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 151: 1548–1561, 1993.PubMedGoogle Scholar
  107. 107.
    Mongkolsapaya, J., A. E. Cowper, X. N. Xu, G. Morris, A. J. McMichael, J. J. Bell, and G. R. Screaton. Lymphocyte inhibitor of TRAIL (TNF-related apoptosis-inducing ligand): a new receptor protecting lymphocytes from the death ligand TRAIL. J Immunol 160: 3–6, 1997.Google Scholar
  108. 108.
    Morinaga, T., N. Nakagawa, T. Yasuda, E. Tsuda, and K. Higashio. Cloning and characterization of the gene encoding human osteoprotegerin/osteoclastogenesis-inhibitory factor. Eur J Biochem 254: 685–691, 1998.PubMedGoogle Scholar
  109. 109.
    Moss, M. L., S. L. C. Jin, M. E. Milla, W. Burkhart, H. L. Carter, W. J. Chen, W. C. Clay, J. R. Didsbury, D. Hassler, C. R. Hoffman, T. A. Kost, M. H. Lambert, M. A. Leesnitzer, P. McCauley, G. McGeehan, J. Mitchell, M. Moyer, G. Pahel, W. Rocque, L. K. Overton, F. Schoenen, T. Seaton, J. L. Su, J. Warner, D. Willard, and J. D. Becherer. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-α. Nature 385: 733–736, 1997.PubMedGoogle Scholar
  110. 110.
    Muellberg, J., F. H. Durie, C. Otten-Evans, M. R. Alderson, S. Rose-John, D. Cosman, R. A. Black, and K. M. Mohler. A metalloprotease inhibitor blocks shedding of the IL-6 receptor and the p60 TNF receptor. J Immunol 155: 5198–5205, 1995.Google Scholar
  111. 111.
    Muzio, M., J. Ni, P. Feng, and V. M. Dixit. IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 278: 1612–1615, 1997.PubMedGoogle Scholar
  112. 112.
    Nagata, S. Fas and Fas ligand: a death factor and its receptor. Adv Immunol 57: 129–-, 1994.PubMedGoogle Scholar
  113. 113.
    Nagata, S., and P. Golstein. The Fas death factor. Science 267: 1449–1456, 1995.PubMedGoogle Scholar
  114. 114.
    Nagato, S. Apoptosis by death factor. Cell 88: 355–365, 1997.Google Scholar
  115. 115.
    Newton, K., A. H. Harris, M. L. Barth, K. G. C. Smith, and A. Strasser. A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. EMBO J 18: 706–718, 1998.Google Scholar
  116. 116.
    Oehm, A., I. Behrmann, W. Falk, M. Pawlita, G. Maier, C. Klas, M. Li-Weber, S. Richards, J. Dhein, B. C. Trauth, H. Ponstingl, and P. H. Krammer. Purification and molecular cloning of the APO-1 cell surface antigen, a new member of the TNF/NGF receptor superfamily: sequence identity with the Fas antigen. J Biol Chem 267: 10709–10715, 1992.PubMedGoogle Scholar
  117. 117.
    Okura, T., L. Gong, T. Kamitani, T. Wada, I. Okura, C. F. Wei, H. M. Chang, and E. T. Yeh. Protection against Fas/Apo-1-and tumor necrosis factor-mediated cell death by a novel protein, sentrin. J Immunol 15: 4277–4288, 1996.Google Scholar
  118. 118.
    Opipari, A. W., H. M. Hu, R. Yabkowitz, and V. M. Dixit. The A20 zinc finger protein protects cells from tumor necrosis factor cytotoxicity. J Biol Chem 267: 12424–12427, 1992.PubMedGoogle Scholar
  119. 119.
    Orlinick, J. R., A. Vaishnaw, K. B. Elkon, and M. v. Chao. Requirement of cysteine-rich repeats of the Fas receptor for binding the Fas ligand. J Biol Chem 272: 28889–28894, 1997.PubMedGoogle Scholar
  120. 120.
    Pan, G., J. H. Bauer, V. Haridas, S. Wang, D. Liu, G. Yu, C. Vincenz, B. B. Aggarwal, J. Ni, and V. M. Dixit. Identification and functional characterization of DR6, a novel death domain-containing TNF receptor. FEBS Lett 431: 351–356, 1998.PubMedGoogle Scholar
  121. 121.
    Pan, G., J. Ni, Y. F. Wei, Q. L. Yu, R. Gentz, and V. M. Dixit. An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277: 815–818, 1997.PubMedGoogle Scholar
  122. 122.
    Pan, G., J. Ni, G. L. Yu, Y. F. Wei, and V. M. Dixit. TRUNDD, a new member of the TRAIL receptor family that antagonizes TRAIL signalling. FEBS Lett 424: 41–45, 1998.PubMedGoogle Scholar
  123. 123.
    Pan, G., K. O’Rourke, A. M. Chinnaiyan, R. Gentz, R. Ebner, J. Ni, and V. M. Dixit. The receptor for the cytotoxic ligand TRAIL. Science 276: 111–113, 1997.PubMedGoogle Scholar
  124. 124.
    Pan, G. H., K. O’Rourke, and V. M. Dixit. Caspase-9, Bcl-xL, and Apaf-1 form a ternary complex. J Biol Chem 273: 5841–5845, 1998.PubMedGoogle Scholar
  125. 125.
    Papoff, G., I. Cascino, A. Eramo, G. Starace, D. H. Lynch, and G. Ruberti. An N-terminal domain shared by Fas/Apo-1 (CD95) soluble variants prevents cell death in vitro. J Immunol 156: 4622–4630, 1996.PubMedGoogle Scholar
  126. 126.
    Pasqualini, R., E. Koivunen, and E. Ruoslahti. A peptide isolated from phage display libraries is a structural and functional mimic of an RGD-binding site on integrins. J Cell Biol 130: 1189–1196, 1995.PubMedGoogle Scholar
  127. 127.
    Peter, M. E., and P. E. Krammer. Mechanisms of CD95 (APO-1/Fas)-mediated apoptosis. Curr Opin Immunol 10: 545–551, 1998.PubMedGoogle Scholar
  128. 128.
    Pitti, R. M., S. A. Marsters, D. A. Lawrence, M. Roy, F. C. Kischkel, P. Dowd, A. Huang, C. J. Donahue, S. W. Sherwood, A. L. Gurney, K. J. Hillan, R. L. Cohen, A. D. Goddard, D. Botstein, and A. Ashkenazi. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 396: 699–703, 1998.PubMedGoogle Scholar
  129. 129.
    Pitti, R. M., S. A. Marsters, S. Ruppert, C. J. Donahue, A. Moore, and A. Ashkenazi. Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 271: 12687–12690, 1996.PubMedGoogle Scholar
  130. 130.
    Ruoslahti, E. RGD and other recognition sequences for integrins. Ann Rev Cell Dev Biol 12: 697–715, 1996.Google Scholar
  131. 131.
    Ruoslahti, E., and J. Reed. New way to activate caspases. Nature 397: 479–480, 1999.PubMedGoogle Scholar
  132. 132.
    Sato, T., S. Irie, S. Kitada, and J. C. Reed. FAP-1: a protein tyrosine phosphatase that associates with Fas. Science 268: 411–415, 1995.PubMedGoogle Scholar
  133. 133.
    Scaffidi, C., S. Fulda, A. Srinivasan, C. Friesen, F. Li, K. J. Tomaselli, K. M. Debatin, P. H. Krammer, and M. E. Peter. Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17: 1675–1687, 1998.PubMedGoogle Scholar
  134. 134.
    Schall, T. J., M. Lewis, K. J. Koller, A. Lee, G. C. Rice, G. H. W. Wong, T. Gatanaga, G. A. Granger, R. Lentz, H. Raab, W. J. Kohr, and D. V. Goeddel. Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell 61: 361–370, 1990.PubMedGoogle Scholar
  135. 135.
    Schneider, P., J. L. Bodmer, M. Thome, K. Hofmann, N. Holler, and J. Tschopp. Characterization of two receptors for TRAIL. FEBS Lett 416: 329–334, 1997.PubMedGoogle Scholar
  136. 136.
    Schneider, P., M. Thome, K. Burns, J. L. Bodmer, K. Hofmann, T. Kataoka, N. Holler, and J. Tschopp. TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kB. Immunity 7: 831–836, 1997.PubMedGoogle Scholar
  137. 137.
    Schreck, R., K. Albermann, and P. A. Baeuerle. Nuclear factor kappa B: an oxidative stress-response transcription factor of eukaryotic cells. Free Rad Res Comm 17: 221–227, 1992.Google Scholar
  138. 138.
    Schuchmann, M., S. Hess, P. Bufler, C. Brakebusch, D. Wallach, A. Porter, G. Riethmuelter, and H. Engelmann. Functional discrepancies between tumor necrosis factor and lymphotoxin α explained by trimer stability and distinct receptor interactions. Eur J Immunol 25: 2183–2189, 1995.PubMedGoogle Scholar
  139. 139.
    Schulze-Osthoff, K., D. Ferrari, M. Los, S. Wesselborg, and M. E. Peter. poptosis signaling by death receptors. Eur J Biochem 254: 439–459, 1998.PubMedGoogle Scholar
  140. 140.
    Schumann, H., H. Morawietz, K. Hakim, H. R. Zerkowski, T. Eschenhagen, J. Holtz, and D. Darmer. Alternative splicing of the primary Fas transcript generating soluble Fas antagonists is suppressed in the failing human ventricular myocardium. Biochem Biophys Res Comm 239: 794–798, 1997.PubMedGoogle Scholar
  141. 141.
    Screaton, G. R., J. Monkolsapaya, X. N. Xu, A. E. Cowper, A. J. McMichael, and J. L. Bell. TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal from TRAIL. CurrBiol 7: 693–696, 1997.Google Scholar
  142. 142.
    Screaton, G. R., X. N. Xu, A. L. Olsen, A. E. Cowper, R. Tan, A. J. McMichael, and J. I. Bell. LARD: a new lymphoid-specific death domain containing receptor regulated by alternative pre-mRNA splicing. Proc Natl Acad Sci 94: 4615–4619, 1997.PubMedGoogle Scholar
  143. 143.
    Sheridan, J. P., S. A. Marsters, R. M. Pitti, A. Gurney, M. Skubatch, D. Baldwin, L. Ramakrishnan, C. L. Gray, K. Baker, W. I. Wood, A. D. Goddard, P. Godowski, and A. Ashkenazi. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277: 818–821, 1997.PubMedGoogle Scholar
  144. 144.
    Shu, H. B., D. R. Halpin, and D. V. Goeddel. Casper is a FADD-and caspase-related inducer of apoptosis. Immunity 6: 751–763, 1997.PubMedGoogle Scholar
  145. 145.
    Shu, H. B., M. Takeuchi, and D. V. Goeddel. The tumor necrosis factor receptor 2 signal transducers TRAF2 and cIAPI are components of the tumor necrosis factor 1 signaling complex. Proc Natl Acad Sci 93: 13973–13978, 1996.PubMedGoogle Scholar
  146. 146.
    Siegel, R. M., D. A. Martin, L. Zheng, S. Y. Ng, J. Berlin, J. Cohen, and M. J. Lenardo. Death-effector filaments: novel cytoplasmic structures that recruit caspases and trigger apoptosis. J Cell Biol 141: 1243–1253, 1998.PubMedGoogle Scholar
  147. 147.
    Simonet, W. S., D. L. Lacey, C. R. Dunstan, M. Kelley, M. S. Chang, R. Luthy, H. Q. Nguyen, S. Wooden, L. Bennett, T. Boone, G. Shimamoto, M. DeRose, R. Elliott, A. Colombero, H. L. Tan, G. Trail, J. Sullivan, E. Davy, N. Bucay, L. Renshaw-Gegg, T. M. Hughes, D. Hill, W. Pattison, P. Campbell, S. Sander, G. Van, J. Tarpley, P. Derby, R. Lee, A. E. Program, and W. J. Boyle. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89: 309–319, 1997.PubMedGoogle Scholar
  148. 148.
    Smith, C. A., T. Davis, D. Anderson, L. Solam, M. P. Beckmann, R. Jerzy, S. K. Dower, D. Cosman, and R. G. Goodwin. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science 248: 1019–1023, 1990.PubMedGoogle Scholar
  149. 149.
    Song, H. Y., J. D. Dunbar, and D. B. Donner. Aggregation of the intracellular domain of the type 1 tumor necrosis factor receptor defined by the two-hybrid system. J Biol Chem 269: 22492–22495, 1994.PubMedGoogle Scholar
  150. 150.
    Srinivasula, S. M., M. Ahmad, S. Ottilie, F. Bullrich, S. Banks, T. Fernandes-Alnemri, C. M. Croce, G. Litwack, K. J. Tomaselli, R. C. Armstrong, and E. S. Ainemeri. FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR 1-induced apoptosis. J Biol Chem 272: 18542–18545, 1997.PubMedGoogle Scholar
  151. 151.
    Stankovski, I., and D. Baltimore. NF-kB activation: the IkB kinase revealed? Cell 91: 299–302, 1997.Google Scholar
  152. 152.
    Steemans, M., V. Goossens, M. Van de Craen, F. Van Heereweghe, K. Vancompernolle, K. De Vos, P. Vandenabeele, and J. Groten. A caspase-activated factor (CAF) induces mitochondrial membrane depolarization and cytochrome c release by a nonproteolytic mechanism. J Exp Med 188: 2193–2198, 1998.PubMedGoogle Scholar
  153. 153.
    Suda, T., T. Takahashi, P. Goldstein, and S. Nagata. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell 75: 1169–1178, 1993.PubMedGoogle Scholar
  154. 154.
    Susin, S. A., H. K. Lorenzo, N. Zamzami, I. Marzo, C. Brenner, N. Larochette, M. C. Prévost, P. M. Aizari, and G. Kroemer. Mitochondrial release of caspase-2 and-9 during the apoptotic process. J Exp Med 189: 381–393, 1999.PubMedGoogle Scholar
  155. 155.
    Susin, S. A., H. K. Lorenzo, N. Zamzami, I. Marzo, B. E. Snow, G. M. Brothers, J. Mangion, E. Jacotot, P. Costantini, M. Loeffier, N. Larochette, D. R. Goodletti, R. Aebersold, D. P. Siderovski, J. M. Penninger, and G. Kroemer. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397: 441–446, 1999.PubMedGoogle Scholar
  156. 156.
    Susin, S. A., N. Zamzami, M. Castedo, T. Hirsch, P. Marchetti, A. Macho, E. Daugas, M. Geuskens, and G. Kroemer. Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J Exp Med 184: 1331–1341, 1996.PubMedGoogle Scholar
  157. 157.
    Susin, S. A., N. Zamzami, and G. Kroemer. Mitochondrial regulation of apoptosis: doubt no more. Biochim Biophys Acta 1366: 151–165, 1998.PubMedGoogle Scholar
  158. 158.
    Tanaka, M., H. Ino, K. Ohno, K. Hattori, W. Sato, T. Ozawa, T. Tanaka and S. Itoyama. Mitochondrial mutation in fatal infantile cardiomyopathy. Lancet 336: 1452, 1990.PubMedGoogle Scholar
  159. 159.
    Tanaka, M., T. Itai, M. Adachi, and S. Nagata. Downregulation of Fas ligand by shedding. Nature Med 4: 31–36, 1998.PubMedGoogle Scholar
  160. 160.
    Tartaglia, A. T., D. Pennica, and D. V. Goeddel. Ligand passing the 75-kDa tumor necrosis factor (TNF) receptor recruits TNF for signaling by the 55-kDa TNF receptor. J Biol Chem 268: 18542–18548, 1993.PubMedGoogle Scholar
  161. 161.
    Tartaglia, L. A., T. M. Ayres, G. H. W. Wong, and D. V. Goeddel. A novel domain within the 55 kD TNF receptor signals cell death. Cell 74: 845–853, 1993.PubMedGoogle Scholar
  162. 162.
    Tartaglia, L. A., M. Rothe, Y. F. Hu, and D. V. Goeddel. Tumor necrosis factor’s cytotoxic activity is signaled by the p55 TNF receptor. Cell 73: 213–216, 1993.PubMedGoogle Scholar
  163. 163.
    Thoma, B., M. Grell, K. Pfizenmaier, and P. Scheurich. Identification of a 60 kDa tumor necrosis factor (TNF) receptor as the major signal transducing component in TNF responses. J Exp Med 172: 1019–1023, 1990.PubMedGoogle Scholar
  164. 164.
    Thornberry, N. A., and Y. Lazebnik. Caspases: enemies within. Science 281: 1313–1316, 1998.Google Scholar
  165. 165.
    Torre-Amione, G., S. Kapadia, J. Lee, J. B. Durand, R. D. Bies, J. B. Young, and D. L. Mann. Tumor necrosis factor-α and tumor necrosis factor receptors in the failing human heart. Circulation 93: 704–711, 1996.PubMedGoogle Scholar
  166. 166.
    Trauth, B. C., C. Klas, A. M. J. Peters, S. Matzku, P. Moeller, W. Falk, K. M. Debatin, and P. H. Krammer. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 245: 301–305, 1989.PubMedGoogle Scholar
  167. 167.
    Tsuda, E., M. Goto, S. I. Mochiguzi, K. Yano, F. Kobayashi, T. Morinaga, and K. Higashio. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem Biophys Res Comm 234: 137–142, 1997PubMedGoogle Scholar
  168. 168.
    Uren, A. G., M. Pakusch, C. J. Hawkins, K. L. Puls, and D. L. Vaux. Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. Proc Natl Acad Sci 93: 4974–4978, 1996.PubMedGoogle Scholar
  169. 169.
    Uren, A. G., and D. L. Vaux. Viral inhibitors of apoptosis. Vitam Horm 53: 175–193, 1997.PubMedGoogle Scholar
  170. 170.
    Van Antwerp, D. J., S. J. Martin, T. Kafri, D. R. Green, and I. M. Verma. Suppression of TNF-α-induced apoptosis by NF-kB. Science 274: 787–789, 1996.PubMedGoogle Scholar
  171. 171.
    Walczak, H., M. A. Degli-Esposti, R. S. Johnson, P. J. Smolak, J. Y. Waugh, N. Bioani, M. S. Timour, M. J. Gerhart, K. A. Schooley, C. A. Smith, R. G. Goodwin, and C. T. Rauch. TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. Embo J 16: 5386–5397, 1997.PubMedGoogle Scholar
  172. 172.
    Wallach, D., A. V. Kovalenko, E. E. Vasfolomeev, and M. P. Boldin. Death-inducing functions of ligands of the tumor necrosis factor family: a Sanhedrin verdict. Curr Opin Immunol 10: 279–288, 1998.PubMedGoogle Scholar
  173. 173.
    Wang, C. Y., M. W. Mayo, and A. S. Baldwin. TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kB. Science 274: 784–787, 1996.PubMedGoogle Scholar
  174. 174.
    Warzowa, K., P. Ribeiro, C. Chariot, N. Renard, B. Coiffier, and G. Salles. A new death receptor 3 isoform: expression in human lymphoid cell lines and non-Hodgkin’s iymphomas. Biochem Biophys Res Comm 242: 376–379, 1998.Google Scholar
  175. 175.
    Weiss, T., M. Grell, K. Siemienski, F. Muhlenbeck, H. Durkop, K. Pfizenmaier, P. Scheurich, and H. Wajant. TNFR80-dependent enhancement of TNFR60-induced cell death is mediated by TNFR60-associated factor 2 and is specific for TNFR60. J Immunol 161: 3136–3142, 1998.PubMedGoogle Scholar
  176. 176.
    Wiegmann, K., S. Schuetze, T. Machleidt, D. Witte, and M. Kroenke. Functional dichotomy of neutral and acidic sphingomyelinases in tumor necrosis factor signaling. Cell 78: 1005–1015, 1994.PubMedGoogle Scholar
  177. 177.
    Wiley, S. R., K. Schooley, P. J. Smolak, W. S. Din, C. P. Huang, J. K. Nicholl, G. R. Sutherland, T. D. Smith, C. Rauch, C. A. Smith, and R. G. Goodwin. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3: 673–682, 1995.PubMedGoogle Scholar
  178. 178.
    Wong, B. R., J. Rho, J. Arron, E. Robinson, J. Orlinick, M. Chao, S. Kalachikov, E. Cayani, F. S. Bartlett, W. N. Frankel, S. Y. Lee, and Y. Choi. TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. J Biol Chem 272: 25190–25194, 1997.PubMedGoogle Scholar
  179. 179.
    Wu, G. S., T. F. Burns, E. R. McDonald, W. Jiang, R. Meng, I. D. Krantz, G. Kao, D. D. Gan, J. Y. Zhou, R. Muschel, S. R. Hamilton, N. B. Spinner, S. Markowitz, G. Wu, and W. S. el-Deiry. Killer/DR5 is DNA damage-inducible p53-regulated death receptor gene. Nature Genet 17: 141–143, 1997.PubMedGoogle Scholar
  180. 180.
    Yamaguchi, K., M. Kinosaki, M. Goto, F. Kobayashi, E. Tsuda, T. Morinaga, and K. Higashio. Characterization of structural domains of osteoclastogenesis inhibitory factor. J Biol Chem 273: 5117–5123, 1998.PubMedGoogle Scholar
  181. 181.
    Yanagisawa, J., M. Takahashi, H. Kanki, H. Yano-Yanagisawa, T. Tazunoki, E. Sawa, T. Nishitoba, M. Kamishohara, E. Kobayashi, S. Kataoka, and T. Sato. The molecular interaction of Fas and FAP-l: a tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis. J Biol Chem 272: 8539–8545, 1997.PubMedGoogle Scholar
  182. 182.
    Yasuda, H., N. Shima, N. Nakagawa, S. I. Mochizuki, K. Yano, N. Fujise, Y. Sato, M. Goto, K. Yamaguchi, M. Kuriyama, T. Kanno, A. Murakami, E. Tsuda, T. Morinaga, and K. Higashio. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG-OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139: 1329–1337, 1998.PubMedGoogle Scholar
  183. 183.
    Yonehara, S., A. Ishii, and M. Yonehara. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen downregulated with the receptor of tumor necrosis factor. J Exp Med 169: 1747–1756, 1989.PubMedGoogle Scholar
  184. 184.
    Yue, T. L., X. L. Ma, X. Wang, A. M. Romanic, G. L. Liu, C. Louden, J. L. Gu, S. Kumar, G. Poste, R. R. Ruffolo, and G. Z. Feuerstein. Possible involvement of stress-activated protein kinase signaling pathway and Fas receptor expression in prevention of ischemia/reperfusion-induced cardiomyocyte apoptosis by carvedilol. Circ Res 82: 166–174, 1998.PubMedGoogle Scholar
  185. 185.
    Zornig, M., A. O. Hueber, and G. Evan. p53-dependent impairment of T-cell proliferation in FADD dominant negative transgenic mice. Curr Biol 8: 467–470, 1998.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Jürgen Holtz
    • 1
  • Dorothea Darmer
    • 1
  1. 1.Martin-Luther-Universität Halle-WittenbergHalle/SaaleGermany

Personalised recommendations