Abstract
Apoptosis, or Programmed Cell Death, is the activation of an inherent cellular suicide program that results in cell death [1]. There are two hallmarks in the death process. First, is a set of distinct morphologic changes such as membrane blebbing, cell shrinkage, and chromosomal condensation followed by chromosomal fragmentation. Second, is the rapid phagocytosis of the corpses of the dead cells, resulting in a limited local immune response. Recently it has been demonstrated that apoptosis plays a crucial role in cardiac damage and a variety of human diseases such as acute liver failure, Alzheimer’s disease, and cancer [2]. The realization that apoptosis constitutes a major mechanism of tumor suppression has dramatically advanced tumor biology by leading to a number of novel approaches for preventing, diagnosing, and treating cancer. The guiding principles for understanding and manipulating the apoptotic response have emerged from studies of both lower eukaryotes and mammalian model systems [3]. These principles, as well as strategies designed to harness the apoptotic response, are described in this chapter.
Keywords
- Death Domain
- Receptor Interact Protein
- Adenine Nucleotide Translocator
- High Conductance State
- Proapoptotic Signal
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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Kerr A, Wyllie AH, Currie AR: Apoptosis: a basic biological phenomenon with wide-ranging implication in tissue kinetics. Br J Cancer 1972, 26:239–257.
Thompson CB: Apoptosis in the pathogenesis and treatment of disease. Science 1995, 267:1456–1462.
Hengartner MO, Horvitz FIR: Programmed cell death in Caenorhabditis elegans. Curr Opin Genet Dev 1994, 4:581–586.
Yuan J, Horvitz HR: The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death. Development 1992, 116:309–320.
Yuan J, Shaham S, Ledoux S, et al.: The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 1993, 75:641–652.
Hengartner MO, Ellis RE, Horvitz HR: Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 1992, 356:494–499.
Shaham S, Horvitz HR: Developing Caenorhabditis elegans neurons may contain both cell-death protective and killer activities. Genes Dev 1996, 10:578–591.
Cryns V, Yuan J: Proteases to die for. Genes Dev 1998, 12:1551–1570.
Adams JM, Cory S: The Bc1–2 protein family: arbiters of cell survival. Science 1998, 281:1322–1326.
Hengartner M: Death by crowd control. Science 1998, 281:1298–1299.
Yang X, Chang HY, Baltimore D: Essential role of CED-4 oligomerization in CED-3 activation and apoptosis [see comments]. Science 1998, 281:1355–1357.
Conradt B, Horvitz HR: The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bc1–2-like protein CED-9. Cell 1998, 93:519–529.
Cohen GM: Caspases: the executioners of apoptosis. Biochem J 1997, 326:1–16.
Ashkenazi A, Dixit VM: Death receptors: signaling and modulation. Science 1998, 281:1305–1308.
Hsu H, Xiong J, Goeddel DV: The TNF receptor 1-associated protein TRADD signals cell death and NF-K B activation. Cell 1995, 81:495–504.
Nagata S: Apoptosis by death factor. Cell 1997, 88:355–365.
Kuida K, Zheng TS, Na S, et al.: Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 1996, 384:368–372.
Kuida K, Haydar TF, Kuan CY, et al.: Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 1998, 94:325–337.
Hakem R, Hakem A, Duncan GS, et al.: Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 1998, 94:339–352.
Zou H, Henzel WJ, Liu X, et al.: Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3 [see comments]. Cell 1997, 90:405–443.
Pan G, O’Rourke K, Dixit VM: Capsase-9, Bcl-XL, and Apaf-1 form a ternary complex. J Biol Chem 1998, 273:5841–5845.
Cecconi F, Alvarez-Bolado G, Meyer BI, et al.: Apafl (CED-4 homolog) regulates programmed cell death in mammalian development. Cell 1998,94:727–737.
Yoshida H, Kong YY, Yoshida R, et al.: Apafl is required for mitochondrial pathways of apoptosis and brain development. Cell 1998, 94:739–750.
Hengartner MO, Horvitz HR: C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bd-2. Cell 1994, 76:665–676.
Kelekar A, Thompson CB: Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biel 1998, 8:324–330.
Wang H-G, Rapp UR, Reed JC: Bd-2 targets the protein kinase Raf-1 to mitochondria. Cell 1996, 87:629–638.
Shibasaki F, Kondo E, Akagi T, McKeon F: Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bc1–2. Nature 1997, 386:728–731.
Hunter JJ, Bond BL, Parslow TG: Functional dissection of the human Bc12 protein: sequence requirements for inhibition of apoptosis. Mol Cell Biel 1996,16:877–883.
Muchmore SW, Sattler M, Liang H, et al.: X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 1996, 381:335–341.
Sattler M, Liang H, Nettesheim D, et al.: Structure of BclxL-Bak peptide complex: recognition between regulators of apoptosis. Science 1997, 275:983–986.
Minn AJ, Velez P, Schendel SL, et al.: Bcl-x(L) forms an ion channel in synthetic lipid membranes. Nature 1997, 385:353–357.
Schendel SL, Xie Z, Montal MO, et al.: Channel formation by antiapoptotic protein Bd-2. Proc Natl Acad Sci U S A 1997, 94:5113–5118.
Schlesinger PH, Gross A, Yin XM, et al.: Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2. Proc Natl Acad Sci U S A 1997, 94:11357–11362.
Vander Heiden MG, Chandel NS, Williamson EK, et al.: Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria [see comments]. Cell 1997, 91:627–637.
Green DR, Reed JC: Mitochondria and apoptosis. Science 1998, 281:1309–1312.
Green DR: Apoptotic pathways: the roads to ruin. Cell 1998, 94:695–698.
Kroemer G, Zamzami N, Susin SA: Mitochondrial control of apoptosis. Immunol Today 1997, 18:44 51.
Marzo I, Brenner C, Zamzami N, et al.: Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science 1998,281:2027–2031.
Antonsson B, Conti F, Ciavatta A, et al.: Inhibition of Bax channel-forming activity by Bd-2. Science 1997, 277:370–372.
Scaffidi C, Fulda S, Srinivasan A, et al.: Two CD95 (APO- 1/Fas) signaling pathways. EMBO J 1998, 17:1675–1687.
Nagata S: Fas-induced apoptosis, and diseases caused by its abnormality. Genes Cells 1996, 1:873–879.
Bennett M, Macdonald K, Chan SW, et al.: Cell surface trafficking of fas: a rapid mechanism of p53-mediated apoptosis. Science 1998, 282:290–293.
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 1995, 81:505–512.
Luo X, Budihardjo I, Zou H, et al.: Bid, a BCL-2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 1998, 94:481–490.
Boldin MP, Goncharov TM, Goltsev YV, Wallach D: Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 1996, 85:803–815.
Muzio M, Chinnaiyan AM, Kischkel FC, et al.: FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell 1996, 85:817–827.
Yang X, Khosravi-Far R, Chang HY, Baltimore D: Daxx, a novel Fas-binding protein that activates JNK and apoptosis. Cell 1997, 89:1067–1076.
Hsu H, Shu HB, Pan MG, Goeddel DV: TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNT receptor 1 signal transduction pathways. Cell 1996, 84:299–308.
Ting AT, Pimentel-Muinos FX, Seed B: RIP mediates tumor necrosis factor receptor 1 activation of NF-KB but not Fas/APO-1-initiated apoptosis. Embo J 1996, 15:6189–6196.
Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin A, Jr.: NF-kappaB antiapoptotis: induction of TRAF1 and TRAF2 and c-IAP1 and c- IAP2 to suppress caspase-8 activation. Science 1998, 281:1680–1683.
Yeh WC, Pompa JL, McCurrach ME, et al.: FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science 1998, 279:1954–1958.
Mang J, Cado D, Chen A, et al.: Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mortl. Nature 1998, 392:296–300.
Marsters SA, Sheridan JP, Pitti RM, et al.: A novel receptor for Apo2L/TRAIL contains a truncated death domain. Curr Biel 1997, 7:1003–1006.
Sheridan JP, Marsters SA, Pitti RM, et al.: Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors [see comments]. Science 1997, 277:818–821.
Irmler M, Thome M, Hahne M, et al.: Inhibition of death receptor signals by cellular FLIP [see comments]. Nature 1997, 388:190–195.
Ambrosini G, Adida C, Altieri DC: A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997, 3:917–921.
Deveraux QL, Takahashi R, Salvesen GS, Reed JC: X-linked 1AP is a direct inhibitor of cell-death proteases. Nature 1997, 388:300–304.
Kimchi A: DAP genes: novel apoptotic genes isolated by a functional approach to gene cloning. Biochim Biophys Acta 1998, 1377:F13–33.
Deiss LP, Kimchi A: A genetic tool used to identify thioredoxin as a mediator of a growth inhibitory signal. Science 1991, 252:117–120.
Deiss LP, Feinstein E, Berissi H, et al.: Identification of a novel serine/threonine kinase and a novel 15-kD protein as potential mediators of the gamma interferon-induced cell death. Genes Dev 1995, 9:15–30.
Inbal B, Cohen O, Polak-Charcon S, et al.: DAP kinase links the control of apoptosis to metastasis. Nature 1997, 390:180–184.
Wu GS, Saftig P, Peters C, El-Deiry WS: Potential role for cathepsin D in p53 dependent tumor suppression and chemosensitivity. Oncogene 1998, 16:2177–2183.
Yang E, Korsmeyer SJ: Molecular thanatopsis: a discourse on the BCL-2 family and cell death. Blood 1996, 88:386–401.
Evan GI, Wyllie AH, Gilbert CS, et al.: Induction of apoptosis in fibroblasts by c-myc protein. Cell 1992, 69:119–128.
Bissonnette RP, Echeverri F, Mahboubi A, Green DR: Apoptotic cell death induced by c-myc is inhibited by bcl2. Nature 1992, 359:552–554.
Fanidi A, Harrington EA, Evan GI: Cooperative interaction between c-myc and bc1–2 proto-oncogenes. Nature 1992, 359:554–556.
Wagner AJ, Small MB, Hay N: Myc-mediated apoptosis is blocked by ectopic expression of Bc1–2. Mol Cell Biol 1993, 13:2432–2440.
Frisch SM, Francis H: Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 1994, 124:619–626.
Frisch SM, Ruoslahti E: Integrins and anoikis. Curr Opin Cell Biol 1997, 9:701–706.
Berry DE, Lu Y, Schmidt B, et al.: Retinoblastoma protein inhibits IFN-gamma induced apoptosis. Oncogene 1996, 12:1809–1819.
Fan G, Ma X, Kren BT, Steer CJ: The retinoblastoma gene product inhibits TGF betal induced apoptosis in primary rat hepatocytes and human HuH-7 hepatoma cells. Oncogene 1996, 12:1909–1919.
Haupt Y, Rowan S, Oren M: p53-mediated apoptosis in HeLa cells can be overcome by excess pRB. Oncogene 1995, 10:1563–1571.
Haas-Kogan DA, Kogan SC, Levi D, et al.: Inhibition of apoptosis by the retinoblastoma gene product. EMBO J 1995, 14:461–472.
Hermeking H, Eick D: Mediation of c-Myc-induced apoptosis by p53. Science 1994, 265:2091–2093.
Wagner AJ, Kokontis JM, Hay N: Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p2lwaf/cipl. Genes Dev 1994, 8:2817–2830.
Kauffmann-Zeh A, Rodriguez-Viciana P, Ulrich E, et al.: Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB. Nature 1997, 385:544–548.
Kennedy SG, Wagner AJ, Conzen SD, et al.: The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev 1997, 11:701–713.
Cantley LC, Neel BG: New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A 1999, 96:4240–4205.
Coffer PJ, Jin J, Woodgett JR: Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem J 1998, 335 (Pt 1):1–13.
Zha J, Harada H, Yang E, et al.: Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14–3–3 not BCL–X(L) [see comments]. Cell 1996, 87:619–628.
Datta SR, Dudek H, Tao X, et al.: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997, 91:231–241.
Maehama T, Dixon JE: The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 1998, 273:13375–13378.
Deiss LP, Galinka H, Berissi H, et al.: Cathepsin D protease mediates programmed cell death induced by interferon-gamma, Fas/APO-1 and TNF-a. Embo J 1996, 15:3861–3870.
Buckbinder L, Talbott R, Velasco-Miguel S, et al.: Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature 1995, 377:646–649.
Miyashita T, Reed JC: Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 1995, 80:293–299.
Jaattela M: Escaping cell death: survival proteins in cancer. Exp Cell Res 1999, 248:30–43.
Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995, 1:27–31.
O’Reilly MS, Holmgren L, Chen C, Folkman J: Angiostatin induces and sustains dormancy of human primary tumors in mice. Nat Med 1996, 2:689–692.
Parangi S, O’Reilly M, Christofori G, et al.: Antiangiogenic therapy of transgenic mice impairs de novo tumor growth. Proc Natl Acad Sci U S A 1996, 93:2002–2007.
Brooks PC, Montgomery AM, Rosenfeld M, et al.: Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 1994, 79:1157–1164.
Brooks PC, Stromblad S, Klemke R, et al.: Antiintegrin alpha AT beta 3 blocks human breast cancer growth and angiogenesis in human skin [see comments]. J Clin Invest 1995, 96:1815–1822.
Brooks PC, Silletti S, von Schalscha TL, et al.: Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell 1998, 92:391–400.
Huang X, Molema G, King S, et al.: Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature [see comments]. Science 1997, 275:547–550.
Strand S, Hofmann WJ, Hug H, et al.: Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand expressing tumor cells-a mechanism of immune evasion? [see comments]. Nat Med 1996, 2:1361–1366.
Hahne M, Rimoldi D, Schroter M, et al.: Melanoma cell expression of Fas(Apo-1 /CD95) ligand: implications for tumor immune escape [see comments]. Science 1996, 274:1363–1366.
Nagata S: Fas ligand and immune evasion [news; comment]. Nat Med 1996, 2:1306–1307.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Current Medicine, Inc.
About this chapter
Cite this chapter
Yehiely, F., Deiss, L.P. (2000). Apoptosis and Cancer. In: Kruh, G.D., Tew, K.D. (eds) Basic Science of Cancer. Current Medicine Group. https://doi.org/10.1007/978-1-4684-8437-3_11
Download citation
DOI: https://doi.org/10.1007/978-1-4684-8437-3_11
Publisher Name: Current Medicine Group
Print ISBN: 978-1-4684-8439-7
Online ISBN: 978-1-4684-8437-3
eBook Packages: Springer Book Archive