Apoptosis: A Way to Maintain Healthy Individuals

Part of the Subcellular Biochemistry book series (SCBI, volume 50)


Apoptosis, the best known form of programmed cell death, is tightly regulated by a number of sensors, signal transducers and effectors. Apoptosis is mainly active during embryonic development, when deletion of redundant cellular material is required for the correct morphogenesis of tissues and organs; moreover, it is essential for the maintenance of tissue homeostasis during cell life. Cells also activate apoptosis when they suffer from various insults, such as damage to DNA or to other cellular components, or impairment of basic processes, such as DNA replication and DNA repair. Removal of damaged cells is fundamental in maintaining the health of organisms. In addition, apoptosis induction following DNA damage is exploited to kill cancer cells. In this chapter we will review the main features of developmental and induced apoptosis.


Aneuploidy Apoptosis Cancer Development Genome instability 



acquired immune deficiency syndrome


apoptosis inducing factor


anaphase promoting complex/cyclosome


cell death abnormal


caspase independent mitotic death


death inducing signaling complex


Down Syndrome


eukaryotic translation elongation factor-1 α1


embryonic stem




spindle assembly checkpoint


tumor necrosis factor-related apoptosis-inducing ligand




  1. Andersen, J. K. (2001) Does neuronal loss in Parkinson’s disease involve programmed cell death? Bioessays, 23, 640–646.PubMedCrossRefGoogle Scholar
  2. Baek, K. H., Shin, H. J., Jeong, S. J., Park, J. W., McKeon, F., Lee, C. W., and Kim, C. M. (2005) Caspases-dependent cleavage of mitotic checkpoint proteins in response to microtubule inhibitor. Oncol Res, 15, 161–168.PubMedGoogle Scholar
  3. Bernardi, R., Negri, C., Donzelli, M., Guano, F., Torti, M., Prosperi, E., and Scovassi, A. I. (1995) Activation of poly(ADP-ribose)polymerase in apoptotic human cells. Biochimie, 77, 378–384.PubMedCrossRefGoogle Scholar
  4. Bidere, N., Su, H. C., and Lenardo, M. J. (2006) Genetic disorders of programmed cell death in the immune system. Annu Rev Immunol, 24, 321–352.PubMedCrossRefGoogle Scholar
  5. Boekelheide, K., Fleming, S. L., Johnson, K. J., Patel, S. R., and Schoenfeld, H. A. (2000) Role of Sertoli cells in injury-associated testicular germ cell apoptosis. Proc Soc Exp Biol Med, 225, 105–115.PubMedCrossRefGoogle Scholar
  6. Bottger, A. and Alexandrova, O. (2007) Programmed cell death in Hydra. Semin Cancer Biol, 17, 134–146.PubMedCrossRefGoogle Scholar
  7. Brito, D. A. and Rieder, C. L. (2006) Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint. Curr Biol, 16, 1194–1200.PubMedCrossRefGoogle Scholar
  8. Cahill, D. P., Lengauer, C., Yu, J., Riggins, G. J., Willson, J. K., Markowitz, S. D., Kinzler, K. W., and Vogelstein, B. (1998) Mutations of mitotic checkpoint genes in human cancers. Nature, 392, 300–303.PubMedCrossRefGoogle Scholar
  9. Call, J. A., Eckhardt, S. G., and Camidge, D. R. (2008) Targeted manipulation of apoptosis in cancer treatment. Lancet Oncol, 9, 1002–1011.PubMedCrossRefGoogle Scholar
  10. Cecconi, F. and Levine, B. (2008) The role of autophagy in mammalian development: cell makeover rather than cell death. Dev Cell, 15, 344–357.PubMedCrossRefGoogle Scholar
  11. Cecconi, F., Piacentini, M., and Fimia, G. M. (2008) The involvement of cell death and survival in neural tube defects: a distinct role for apoptosis and autophagy? Cell Death Differ, 15, 1170–1177.PubMedCrossRefGoogle Scholar
  12. Chandhok, N. S. and Pellman, D. (2009) A little CIN may cost a lot: revisiting aneuploidy and cancer. Curr Opin Genet Dev, 19, 74–81.PubMedCrossRefGoogle Scholar
  13. Checchi, P. M., Nettles, J. H., Zhou, J., Snyder, J. P., and Joshi, H. C. (2003) Microtubule-interacting drugs for cancer treatment. Trends Pharmacol Sci, 24, 361–365.PubMedCrossRefGoogle Scholar
  14. Chiarugi, A. (2002) Poly(ADP-ribose) polymerase: killer or conspirator? The ‘suicide hypothesis’ revisited. Trends Pharmacol Sci, 23, 122–129.PubMedCrossRefGoogle Scholar
  15. Counis, M. F. and Torriglia, A. (2006) Acid DNases and their interest among apoptotic endonucleases. Biochimie, 88, 1851–1858.PubMedCrossRefGoogle Scholar
  16. de Felici, M., Lobascio, A. M., and Klinger, F. G. (2008) Cell death in fetal oocytes: many players for multiple pathways. Autophagy, 4, 240–242.PubMedGoogle Scholar
  17. Degrassi, F., Fiore, M., and Palitti, F. (2004) Chromosomal aberrations and genomic instability induced by topoisomerase-targeted antitumour drugs. Curr Med Chem Anticanc Agents, 4, 317–325.CrossRefGoogle Scholar
  18. Degterev, A. and Yuan, J. (2008) Expansion and evolution of cell death programmes. Nat Rev Mol Cell Biol, 9, 378–390.PubMedCrossRefGoogle Scholar
  19. Duesberg, P. (2007) Chromosomal chaos and cancer. Sci Am, 296, 52–59.PubMedCrossRefGoogle Scholar
  20. Ellis, R. E., Yuan, J. Y., and Horvitz, H. R. (1991) Mechanisms and functions of cell death. Annu Rev Cell Biol, 7, 663–698.PubMedCrossRefGoogle Scholar
  21. Erwig, L. P. and Henson, P. M. (2007) Immunological consequences of apoptotic cell phagocytosis. Am J Pathol, 171, 2–8.PubMedCrossRefGoogle Scholar
  22. Fadeel, B. and Orrenius, S. (2005) Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease. J Intern Med, 258, 479–517.PubMedCrossRefGoogle Scholar
  23. Fan, Y. and Bergmann, A. (2008) Apoptosis-induced compensatory proliferation. The Cell is dead. Long live the Cell! Trends Cell Biol, 18, 467–473.PubMedCrossRefGoogle Scholar
  24. Fink, S. L. and Cookson, B. T. (2005) Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun, 73, 1907–1916.PubMedCrossRefGoogle Scholar
  25. Frouin, I. and Scovassi, A. I. (2008) Poly(ADP-ribosylation) regulates DNA replication and repair. In: Maga G., Hübscher, U. and Villani, G. (Eds.) DNA Replication Repair and Recombination at the Crossroad Between Genome Integrity and Genomic Instability: A Biochemical Perspective, Research Signpost, Kerala, India, pp. 116–130.Google Scholar
  26. Gartner, A., Boag, P. R., and Blackwell, T. K. (2008) Germline survival and apoptosis. WormBook, 1–20.Google Scholar
  27. Ghafari, F., Gutierrez, C. G., and Hartshorne, G. M. (2007) Apoptosis in mouse fetal and neonatal oocytes during meiotic prophase one. BMC Dev Biol, 7, 87.PubMedCrossRefGoogle Scholar
  28. Giansanti, V. and Scovassi, A. I. (2008a) Apoptosis and cancer. In: Mondello C. (Ed.) Multiple Pathways in Cancer Development, Transworld Research Network, Kerala, India, pp. 135–147.Google Scholar
  29. Giansanti, V. and Scovassi, A. I. (2008b) Cell death: a one-way journey to the graveyard. Open Biol J, 1, 27–34.CrossRefGoogle Scholar
  30. Gil, J. M. and Rego, A. C. (2008) Mechanisms of neurodegeneration in Huntington’s disease. Eur J Neurosci, 27, 2803–2820.PubMedCrossRefGoogle Scholar
  31. Giovannetti, A., Pierdominici, M., Di Iorio, A., Cianci, R., Murdaca, G., Puppo, F., Pandolfi, F., and Paganelli, R. (2008) Apoptosis in the homeostasis of the immune system and in human immune mediated diseases. Curr Pharm Des, 14, 253–268.PubMedCrossRefGoogle Scholar
  32. Gougeon, M. L. (2003) Apoptosis as an HIV strategy to escape immune attack. Nat Rev Immunol, 3, 392–404.PubMedCrossRefGoogle Scholar
  33. Gougeon, M. L. and Montagnier, L. (1992) New concepts in the mechanisms of CD4+ lymphocyte depletion in Aids, and the influence of opportunistic infections. Res Microbiol, 143, 362–368.PubMedCrossRefGoogle Scholar
  34. Gougeon, M. L. and Montagnier, L. (1993) Apoptosis in AIDS. Science, 260, 1269–1270.PubMedCrossRefGoogle Scholar
  35. Green, D. R. (2005) Apoptotic pathways: ten minutes to dead. Cell, 121, 671–674.PubMedCrossRefGoogle Scholar
  36. Gregory, C. D. and Brown, S. B. (2005) Apoptosis: eating sensibly. Nat Cell Biol, 7, 1161–1163.PubMedCrossRefGoogle Scholar
  37. Ha, G. H., Baek, K. H., Kim, H. S., Jeong, S. J., Kim, C. M., McKeon, F., and Lee, C. W. (2007) p53 activation in response to mitotic spindle damage requires signaling via BubR1-mediated phosphorylation. Cancer Res, 67, 7155–7164.PubMedCrossRefGoogle Scholar
  38. Hassa, P. O. (2009) The molecular “Jekyll and Hyde” duality of PARP1 in cell death and cell survival. Front Biosci, 14, 72–111.PubMedCrossRefGoogle Scholar
  39. Hay, B. A. and Guo, M. (2006) Caspase-dependent cell death in Drosophila. Annu Rev Cell Dev Biol, 22, 623–650.PubMedCrossRefGoogle Scholar
  40. Hong, Y., Cervantes, R. B., Tichy, E., Tischfield, J. A., and Stambrook, P. J. (2007) Protecting genomic integrity in somatic cells and embryonic stem cells. Mutat Res, 614, 48–55.PubMedGoogle Scholar
  41. Jaattela, M. (1999) Escaping cell death: survival proteins in cancer. Exp Cell Res, 248, 30–43.PubMedCrossRefGoogle Scholar
  42. Jaattela, M. (2004) Multiple cell death pathways as regulators of tumour initiation and progression. Oncogene, 23, 2746–2756.PubMedCrossRefGoogle Scholar
  43. Jacobson, M. D., Weil, M., and Raff, M. C. (1997) Programmed cell death in animal development. Cell, 88, 347–354.PubMedCrossRefGoogle Scholar
  44. Jeggo, P. A. (1998) DNA repair: PARP – another guardian angel?. Curr Biol, 8, R49–R51.PubMedCrossRefGoogle Scholar
  45. Johnson, L., Thompson, D. L., Jr., and Varner, D. D. (2008) Role of Sertoli cell number and function on regulation of spermatogenesis. Anim Reprod Sci, 105, 23–51.PubMedCrossRefGoogle Scholar
  46. Kanai, M., Hanashiro, K., Kim, S. H., Hanai, S., Boulares, A. H., Miwa, M., and Fukasawa, K. (2007) Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation. Nat Cell Biol, 9, 1175–1183.PubMedCrossRefGoogle Scholar
  47. Kaufmann, S. H. (1998) Cell death induced by topoisomerase-targeted drugs: more questions than answers. Biochim Biophys Acta, 1400, 195–211.PubMedGoogle Scholar
  48. Kerr, J. F., Wyllie, A. H., and Currie, A. R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer, 26, 239–257.PubMedGoogle Scholar
  49. Kim, M., Liao, J., Dowling, M. L., Voong, K. R., Parker, S. E., Wang, S., El-Deiry, W. S., and Kao, G. D. (2008) TRAIL inactivates the mitotic checkpoint and potentiates death induced by microtubule-targeting agents in human cancer cells. Cancer Res, 68, 3440–3449.PubMedCrossRefGoogle Scholar
  50. Kim, M., Murphy, K., Liu, F., Parker, S. E., Dowling, M. L., Baff, W., and Kao, G. D. (2005) Caspase-mediated specific cleavage of BubR1 is a determinant of mitotic progression. Mol Cell Biol, 25, 9232–9248.PubMedCrossRefGoogle Scholar
  51. Kim, M. R. and Tilly, J. L. (2004) Current concepts in Bcl-2 family member regulation of female germ cell development and survival. Biochim. Biophys Acta, 1644, 205–210.CrossRefGoogle Scholar
  52. Kobayashi, Y. and Yonehara, S. (2009) Novel cell death by downregulation of eEF1A1 expression in tetraploids. Cell Death Differ, 16, 139–150.PubMedCrossRefGoogle Scholar
  53. Kotani, S., Tanaka, H., Yasuda, H., and Todokoro, K. (1999) Regulation of APC activity by phosphorylation and regulatory factors. J Cell Biol, 146, 791–800.PubMedCrossRefGoogle Scholar
  54. Kumar, S. (2007) Caspase function in programmed cell death. Cell Death Differ, 14, 32–43.PubMedCrossRefGoogle Scholar
  55. Lengauer, C., Kinzler, K. W., and Vogelstein, B. (1998) Genetic instabilities in human cancers. Nature, 396, 643–649.PubMedCrossRefGoogle Scholar
  56. Letai, A. G. (2008) Diagnosing and exploiting cancer’s addiction to blocks in apoptosis. Nat Rev Cancer, 8, 121–132.PubMedCrossRefGoogle Scholar
  57. Levine, B. and Kroemer, G. (2008) Autophagy in the pathogenesis of disease. Cell, 132, 27–42.PubMedCrossRefGoogle Scholar
  58. Li, J. and Yuan, J. (2008) Caspases in apoptosis and beyond. Oncogene, 27, 6194–6206.PubMedCrossRefGoogle Scholar
  59. Liu, Q., Hilsenbeck, S., and Gazitt, Y. (2003) Arsenic trioxide-induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL. Blood, 101, 4078–4087.PubMedCrossRefGoogle Scholar
  60. Lockshin, R. A. and Zakeri, Z. (2004) Apoptosis, autophagy, and more. Int J Biochem Cell Biol, 36, 2405–2419.PubMedCrossRefGoogle Scholar
  61. Luthi, A. U. and Martin, S. J. (2007) The CASBAH: a searchable database of caspase substrates. Cell Death Differ, 14, 641–650.PubMedCrossRefGoogle Scholar
  62. Maiuri, M. C., Le Toumelin, G., Criollo, A., Rain, J. C., Gautier, F., Juin, P., Tasdemir, E., Pierron, G., Troulinaki, K., Tavernarakis, N., Hickman, J. A., Geneste, O., and Kroemer, G. (2007) Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J, 26, 2527–2539.PubMedCrossRefGoogle Scholar
  63. Malanga, M. and Althaus, F. R. (2005) The role of poly(ADP-ribose) in the DNA damage signaling network. Biochem Cell Biol, 83, 354–364.PubMedCrossRefGoogle Scholar
  64. Mathew, R., Kongara, S., Beaudoin, B., Karp, C. M., Bray, K., Degenhardt, K., Chen, G., Jin, S., and White, E. (2007) Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev, 21, 1367–1381.PubMedCrossRefGoogle Scholar
  65. Mathew, R. and White, E. (2007) Why sick cells produce tumors: the protective role of autophagy. Autophagy, 3, 502–505.PubMedGoogle Scholar
  66. Mattson, M. P. (2000) Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol, 1, 120–129.PubMedCrossRefGoogle Scholar
  67. Matulis, S. and Handel, M. A. (2006) Spermatocyte responses in vitro to induced DNA damage. Mol Reprod Dev, 73, 1061–1072.PubMedCrossRefGoogle Scholar
  68. McClendon, A. K. and Osheroff, N. (2007) DNA topoisomerase Ii, genotoxicity, and cancer. Mutat Res, 623, 83–97.PubMedGoogle Scholar
  69. McNeely, S. C., Taylor, B. F., and States, J. C. (2008) Mitotic arrest-associated apoptosis induced by sodium arsenite in A375 melanoma cells is BUBR1-dependent. Toxicol Appl Pharmacol, 231, 61–67.PubMedCrossRefGoogle Scholar
  70. Meraldi, P., Draviam, V. M., and Sorger, P. K. (2004) Timing and checkpoints in the regulation of mitotic progression. Dev Cell, 7, 45–60.PubMedCrossRefGoogle Scholar
  71. Metzstein, M. M., Stanfield, G. M., and Horvitz, H. R. (1998) Genetics of programmed cell death in C. elegans: past, present and future. Trends Genet, 14, 410–416.PubMedCrossRefGoogle Scholar
  72. Meulmeester, E. and Jochemsen, A. G. (2008) p53: a guide to apoptosis. Curr Cancer Drug Targets, 8, 87–97.PubMedCrossRefGoogle Scholar
  73. Montecucco, A. and Biamonti, G. (2007) Cellular response to etoposide treatment. Cancer Lett, 252, 9–18.PubMedCrossRefGoogle Scholar
  74. Negri, C., Bernardi, R., Braghetti, A., Ricotti, G. C., and Scovassi, A. I. (1993) The effect of the chemotherapeutic drug VP-16 on poly(ADP-ribosylation) in apoptotic HeLa cells. Carcinogenesis, 14, 2559–2564.PubMedCrossRefGoogle Scholar
  75. Negri, C., Bernardi, R., Donzelli, M., and Scovassi, A. I. (1995) Induction of apoptotic cell death by DNA topoisomerase II inhibitors. Biochimie, 77, 893–898.Google Scholar
  76. Niikura, Y., Dixit, A., Scott, R., Perkins, G., and Kitagawa, K. (2007) BUB1 mediation of caspase-independent mitotic death determines cell fate. J Cell Biol, 178, 283–296.PubMedCrossRefGoogle Scholar
  77. Nutt, L. K., Margolis, S. S., Jensen, M., Herman, C. E., Dunphy, W. G., Rathmell, J. C., and Kornbluth, S. (2005) Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. Cell, 123, 89–103.PubMedCrossRefGoogle Scholar
  78. Oberst, A., Bender, C., and Green, D. R. (2008) Living with death: the evolution of the mitochondrial pathway of apoptosis in animals. Cell Death Differ, 15, 1139–1146.PubMedCrossRefGoogle Scholar
  79. Oei, S. L., Keil, C., and Ziegler, M. (2005) Poly(ADP-ribosylation) and genomic stability. Biochem Cell Biol, 83, 263–269.PubMedCrossRefGoogle Scholar
  80. Panvichian, R., Orth, K., Day, M. L., Day, K. C., Pilat, M. J., and Pienta, K. J. (1998) Paclitaxel-associated multimininucleation is permitted by the inhibition of caspase activation: a potential early step in drug resistance. Cancer Res, 58, 4667–4672.PubMedGoogle Scholar
  81. Penaloza, C., Orlanski, S., Ye, Y., Entezari-Zaher, T., Javdan, M., and Zakeri, Z. (2008) Cell death in mammalian development. Curr Pharm Des, 14, 184–196.PubMedCrossRefGoogle Scholar
  82. Perera, D. and Freire, R. (2005) Human spindle checkpoint kinase Bub1 is cleaved during apoptosis. Cell Death Differ, 12, 827–830.PubMedCrossRefGoogle Scholar
  83. Pietsch, E. C., Sykes, S. M., McMahon, S. B., and Murphy, M. E. (2008) The p53 family and programmed cell death. Oncogene, 27, 6507–6521.PubMedCrossRefGoogle Scholar
  84. Ricke, R. M., van Ree, J. H., and van Deursen, J. M. (2008) Whole chromosome instability and cancer: a complex relationship. Trends Genet, 24, 457–466.PubMedCrossRefGoogle Scholar
  85. Rieder, C. L. and Maiato, H. (2004) Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint. Dev Cell, 7, 637–651.PubMedCrossRefGoogle Scholar
  86. Riley, T., Sontag, E., Chen, P., and Levine, A. (2008) Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol, 9, 402–412.PubMedCrossRefGoogle Scholar
  87. Rodier, F., Campisi, J., and Bhaumik, D. (2007) Two faces of p53: aging and tumor suppression. Nucleic Acids Res, 35, 7475–7484.PubMedCrossRefGoogle Scholar
  88. Rosen, A. and Casciola-Rosen, L. (1999) Autoantigens as substrates for apoptotic proteases: implications for the pathogenesis of systemic autoimmune disease. Cell Death Differ, 6, 6–12.PubMedCrossRefGoogle Scholar
  89. Rovere-Querini, P., Brunelli, S., Clementi, E., and Manfredi, A. A. (2008) Cell death: Tipping the balance of autoimmunity and tissue repair. Curr Pharm Des, 14, 269–277.PubMedCrossRefGoogle Scholar
  90. Sawa, A. (1999) Neuronal cell death in Down’s syndrome. J Neural Transm Suppl, 57, 87–97.PubMedGoogle Scholar
  91. Schreiber, V., Dantzer, F., Ame, J. C., and de Murcia, G. (2006) Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol, 7, 517–528.PubMedCrossRefGoogle Scholar
  92. Scovassi, A. I., Denegri, M., Donzelli, M., Rossi, L., Bernardi, R., Mandarino, A., Frouin, I., and Negri, C. (1998) Poly(ADP-ribose) synthesis in cells undergoing apoptosis: an attempt to face death before PARP degradation. Eur J Histochem, 42, 251–258.PubMedGoogle Scholar
  93. Scovassi, A. I. and Poirier, G. G. (1999) Poly(ADP-ribosylation) and apoptosis. Mol Cell Biochem, 199, 125–137.PubMedCrossRefGoogle Scholar
  94. Scovassi, A. I. (2002) Multiple roles of poly(ADP-ribosylation. Recent Res Devel Prot, 1, 345–360.Google Scholar
  95. Scovassi, A. I. and Torriglia, A. (2003) Activation of DNA-degrading enzymes during apoptosis. Eur J Histochem, 47, 185–194.PubMedGoogle Scholar
  96. Scovassi, A. I. and Diederich, M. (2004) Modulation of poly(ADP-ribosylation) in apoptotic cells. Biochem Pharmacol, 68, 1041–1047.CrossRefGoogle Scholar
  97. Scovassi, A. I. (2005) Caspase-dependent apoptosis. In: Scovassi A. I. (ed.) Apoptosis, Research Signpost, Kerala, India, pp. 41–55.Google Scholar
  98. Scovassi, A. I. (2006) Apoptosis and cell death. In: Torriglia, A. and Lassiaz, P. (Eds.) Apoptosis in the Retina, Transworld Research Network, Kerala, India, pp. 1–11.Google Scholar
  99. Shi, Y. (2004) Caspase activation: revisiting the induced proximity model. Cell, 117, 855–858.PubMedCrossRefGoogle Scholar
  100. Soldani, C., Lazze, M. C., Bottone, M. G., Tognon, G., Biggiogera, M., Pellicciari, C. E., and Scovassi, A. I. (2001) Poly(ADP-ribose) polymerase cleavage during apoptosis: when and where?. Exp Cell Res, 269, 193–201.PubMedCrossRefGoogle Scholar
  101. Soldani, C. and Scovassi, A. I. (2002) Poly(ADP-ribose) polymerase-1 cleavage during apoptosis: an update. Apoptosis, 7, 321–328.PubMedCrossRefGoogle Scholar
  102. Sordet, O., Khan, Q. A., Kohn, K. W., and Pommier, Y. (2003) Apoptosis induced by topoisomerase inhibitors. Curr Med Chem Anticancer Agents, 3, 271–290.PubMedCrossRefGoogle Scholar
  103. States, J. C., Reiners, J. J., Jr., Pounds, J. G., Kaplan, D. J., Beauerle, B. D., McNeely, S. C., Mathieu, P., and McCabe, M. J., Jr. (2002) Arsenite disrupts mitosis and induces apoptosis in SV40-transformed human skin fibroblasts. Toxicol Appl Pharmacol, 180, 83–91.PubMedCrossRefGoogle Scholar
  104. Steller, H. (2008) Regulation of apoptosis in Drosophila. Cell Death Differ, 15, 1132–1138.PubMedCrossRefGoogle Scholar
  105. Suijkerbuijk, S. J. and Kops, G. J. (2008) Preventing aneuploidy: the contribution of mitotic checkpoint proteins. Biochim Biophys Acta, 1786, 24–31.PubMedGoogle Scholar
  106. Takuma, K., Yan, S. S., Stern, D. M., and Yamada, K. (2005) Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer’s disease. J Pharmacol Sci, 97, 312–316.PubMedCrossRefGoogle Scholar
  107. Tao, W., South, V. J., Zhang, Y., Davide, J. P., Farrell, L., Kohl, N. E., Sepp-Lorenzino, L., and Lobell, R. B. (2005) Induction of apoptosis by an inhibitor of the mitotic kinesin KSP requires both activation of the spindle assembly checkpoint and mitotic slippage. Cancer Cell, 8, 49–59.PubMedCrossRefGoogle Scholar
  108. Thorburn, A. (2008) Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis, 13, 1–9.PubMedCrossRefGoogle Scholar
  109. Tichy, E. D. and Stambrook, P. J. (2008) DNA repair in murine embryonic stem cells and differentiated cells. Exp Cell Res, 314, 1929–1936.PubMedCrossRefGoogle Scholar
  110. Tilly, J. L. (2001) Commuting the death sentence: how oocytes strive to survive. Nat Rev Mol Cell Biol, 2, 838–848.PubMedCrossRefGoogle Scholar
  111. Vakifahmetoglu, H., Olsson, M., and Zhivotovsky, B. (2008) Death through a tragedy: mitotic catastrophe. Cell Death Differ, 15, 1153–1162.PubMedCrossRefGoogle Scholar
  112. Vaux, D. L. and Korsmeyer, S. J. (1999) Cell death in development. Cell, 96, 245–254.PubMedCrossRefGoogle Scholar
  113. Vazquez, A., Bond, E. E., Levine, A. J., and Bond, G. L. (2008) The genetics of the p53 pathway, apoptosis and cancer therapy. Nat Rev Drug Discov, 7, 979–987.PubMedCrossRefGoogle Scholar
  114. Vila, M. and Przedborski, S. (2003) Targeting programmed cell death in neurodegenerative diseases. Nat Rev Neurosci, 4, 365–375.PubMedCrossRefGoogle Scholar
  115. Wiseman, F. K., Alford, K. A., Tybulewicz, V. L., and Fisher, E. M. (2009) Down syndrome–recent progress and future prospects. Hum Mol Genet, 18, R75–R83.PubMedCrossRefGoogle Scholar
  116. Won, J., Chung, S. Y., Kim, S. B., Byun, B. H., Yoon, Y. S., and Joe, C. O. (2006) Dose-dependent UV stabilization of p53 in cultured human cells undergoing apoptosis is mediated by poly(ADP-ribosyl)ation. Mol Cells, 21, 218–223.PubMedGoogle Scholar
  117. Wu, Y. C., Yen, W. Y., and Yih, L. H. (2008) Requirement of a functional spindle checkpoint for arsenite-induced apoptosis. J Cell Biochem, 105, 678–687.PubMedCrossRefGoogle Scholar
  118. Yih, L. H. and Lee, T. C. (2000) Arsenite induces p53 accumulation through an ATM-dependent pathway in human fibroblasts. Cancer Res, 60, 6346–6352.PubMedGoogle Scholar
  119. Yonish-Rouach, E., Resnitzky, D., Lotem, J., Sachs, L., Kimchi, A., and Oren, M. (1991) Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature, 352, 345–347.PubMedCrossRefGoogle Scholar
  120. Zakeri, Z. and Lockshin, R. A. (2002) Cell death during development. J Immunol Meth, 265, 3–20.CrossRefGoogle Scholar
  121. Zhang, N., Hartig, H., Dzhagalov, I., Draper, D., and He, Y. W. (2005) The role of apoptosis in the development and function of T lymphocytes. Cell Res, 15, 749–769.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Istituto di Genetica Molecolare, CNRPaviaItaly

Personalised recommendations