Skip to main content
SpringerLink
Log in

Apoptosis: Pathways, Molecules and Beyond

  • Chapter
Proteases in Apoptosis: Pathways, Protocols and Translational Advances

Abstract

Programmed cell death or apoptosis manifests itself through a complex network of biochemical pathways and distinct morphological signatures. It is a natural phenomenon in multicellular organisms required to maintain tissue homeostasis through selective removal of ageing and unwanted cells. Impairment of this tightly regulated cellular process leads to various pathophysiological conditions including neurodegenerative disorders, ischemic damage, acquired immunodeficiency syndrome and cancer. Recognizing its immense therapeutic potential, a plethora of research endeavors has been undertaken in the past two decades that target molecules involved in apoptosis. Caspases, a conserved family of cysteinyl proteases that initiate and execute programmed cell death through extrinsic and intrinsic pathways are major focus of apoptosis research. However, study of molecules associated with lesser-known caspase-independent cell death is slowly gaining prominence, especially in cases where the traditional pathways fail to activate apoptosis. The goal of this chapter is to provide a broad overview of different apoptotic pathways, molecules involved and their crosstalk with special emphasis on proteases. This chapter also discusses different diseases associated with deregulation of apoptosis, current status on pre-clinical and clinical trials, their limitations and future prospects.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Duque-Parra J (2005) Note on the origin and history of the term “apoptosis”. Anat Rec B New Anat 283:2–4

    PubMed  Google Scholar 

  2. Raff M (1998) Cell suicide for beginners. Nature 396:119–122

    CAS  PubMed  Google Scholar 

  3. Lawen A (2003) Apoptosis-an introduction. Bioessays 25:888–896

    CAS  PubMed  Google Scholar 

  4. Ozoren N, El-Deiry W (2003) Cell surface Death Receptor signaling in normal and cancer cells. Semin Cancer Biol 13:135–147

    PubMed  Google Scholar 

  5. Thorburn A (2004) Death receptor-induced cell killing. Cell Signal 16:139–144

    CAS  PubMed  Google Scholar 

  6. Peter M, Krammer P (1998) Mechanisms of CD95 (APO-1/Fas)-mediated apoptosis. Curr Opin Immunol 10:545–551

    CAS  PubMed  Google Scholar 

  7. Strasser A, O’Connor L, Dixit V (2000) Apoptosis signaling. Annu Rev Biochem 69:217–245

    CAS  PubMed  Google Scholar 

  8. Degli Esposti M (1999) To die or not to die—the quest of the TRAIL receptors. J Leukoc Biol 65:535–542

    CAS  PubMed  Google Scholar 

  9. Abe K, Kurakin A, Mohseni-Maybodi M, Kay B, Khosravi-Far R (2000) The complexity of TNFrelated apoptosis-inducing ligand. Ann N Y Acad Sci 926:52–63

    CAS  PubMed  Google Scholar 

  10. Sharp A, Heazell A, Crocker I, Mor G (2010) Placental apoptosis in health and disease. Am J Reprod Immunol 64:159–169

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Zornig M, Hueber A, Baum W, Evan G (2001) Apoptosis regulators and their role in tumorigenesis. Biochim Biophys Acta 1551:F1–F37

    CAS  PubMed  Google Scholar 

  12. Daniel P, Wieder T, Sturm I, Schulze-Osthoff K (2001) The kiss of death: promises and failures of death receptors and ligands in cancer therapy. Leukemia 15:1022–1032

    CAS  PubMed  Google Scholar 

  13. Green D, Evan G (2002) A matter of life and death. Cancer Cell 1:19–30

    CAS  PubMed  Google Scholar 

  14. Thompson C (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267:1456–1462

    CAS  PubMed  Google Scholar 

  15. Sheikh M, Huang Y (2004) Death receptors as targets of cancer therapeutics. Curr Cancer Drug Targets 4:97–104

    CAS  PubMed  Google Scholar 

  16. Burns T, el-Deiry W (2003) Cell death signaling in maligancy. Cancer Treat Res 115:319–343

    CAS  PubMed  Google Scholar 

  17. Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Philchenkov A (2004) Caspases: potential targets for regulating cell death. J Cell Mol Med 8:432–444

    CAS  PubMed  Google Scholar 

  19. Lushnikov EF, Zagrebin VM (1987) Cellular apoptosis: its morphology, biological role and the mechanisms of its development. Arkh Patol 49:84–89

    CAS  PubMed  Google Scholar 

  20. Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306

    CAS  PubMed  Google Scholar 

  21. Jin Z, El-Deiry WS (2005) Overview of cell death signaling pathways. Cancer Biol Ther 4:139–163

    CAS  PubMed  Google Scholar 

  22. Schultz DR, Harrington WJ Jr (2003) Apoptosis: programmed cell death at a molecular level. Semin Arthritis Rheum 32:345–369

    CAS  PubMed  Google Scholar 

  23. Askkenazi A, Dixit V (1999) Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 11:255–260

    Google Scholar 

  24. Naismith JH, Sprang SR (1998) Modularity in the TNF-receptor family. Trends Biochem Sci 23:74–79

    CAS  PubMed  Google Scholar 

  25. Schneider P, Tschopp J (2000) Apoptosis induced by death receptors. Pharm Acta Helv 74:281–286

    CAS  PubMed  Google Scholar 

  26. Salvesen GS, Dixit VM (1999) Caspase activation: the induced-proximity model. Proc Natl Acad Sci U S A 96:10964–10967

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Logue S, Martin S (2008) Caspase activation cascades in apoptosis. Biochem Soc Trans 36:1–9

    CAS  PubMed  Google Scholar 

  28. Ferreira K, Clemens K, MacNelly S, Neubert K, Haber A, Bogyo M, Timmer J, Borner C (2012) Caspase-3 feeds back on caspase-8, Bid and XIAP in type I Fas signaling in primary mouse hepatocytes. Apoptosis 17:503–515

    CAS  PubMed  Google Scholar 

  29. Cohen GM (1997) Caspases: the executioners of apoptosis. Biochem J 326(Pt 1):1–16

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Safa AR (2012) c-FLIP, a master anti-apoptotic regulator. Exp Oncol 34:176–184

    CAS  PubMed  Google Scholar 

  31. Silke J, Meier P (2013) Inhibitor of apoptosis (IAP) proteins-modulators of cell death and inflammation. Cold Spring Harb Perspect Biol 5(2):a008730

    Google Scholar 

  32. Tartaglia L, Ayres T, Wong G, Goeddel D (1993) A novel domain within the 55 kd TNF receptor signals cell death. Cell 74:845–853

    CAS  PubMed  Google Scholar 

  33. Hsu H, Xiong J, Goeddel D (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81:495–504

    CAS  PubMed  Google Scholar 

  34. Chan FK (2007) Three is better than one: pre-ligand receptor assembly in the regulation of TNF receptor signaling. Cytokine 37:101–107

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Chan FK, Chun HJ, Zheng L, Siegel RM, Bui KL, Lenardo MJ (2000) A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science 288:2351–2354

    CAS  PubMed  Google Scholar 

  36. Jiang Y, Woronicz J, Liu W, Goeddel D (1999) Prevention of constitutive TNF receptor 1 signaling by silencer of death domains. Science 283:543–546

    CAS  PubMed  Google Scholar 

  37. Di Pietro R, Zauli G (2004) Emerging non-apoptotic functions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2L. J Cell Physiol 201:331–340

    PubMed  Google Scholar 

  38. Nagata S (1999) FAS ligand-induced apoptosis. Annu Rev Genet 33:29–55

    CAS  PubMed  Google Scholar 

  39. Sessler T, Healy S, Samali A, Szegezdi E (2013) Structural determinants of DISC function: new insights into death receptor-mediated apoptosis signalling. Pharmacol Ther 140:186–199

    CAS  PubMed  Google Scholar 

  40. Yan Q, McDonald JM, Zhou T, Song Y (2013) Structural insight for the roles of fas death domain binding to FADD and oligomerization degree of the Fas-FADD complex in the death-inducing signaling complex formation: a computational study. Proteins 81:377–385

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Wang L, Yang JK, Kabaleeswaran V, Rice AJ, Cruz AC, Park AY, Yin Q, Damko E, Jang SB, Raunser S, Robinson CV, Siegel RM, Walz T, Wu H (2010) The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations. Nat Struct Mol Biol 17:1324–1329

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Stennicke H, Salvesen G (2000) Caspases – controlling intracellular signals by protease zymogen activation. Biochim Biophys Acta 1477:299–306

    CAS  PubMed  Google Scholar 

  43. Wang J, Chun HJ, Wong W, Spencer DM, Lenardo MJ (2001) Caspase-10 is an initiator caspase in death receptor signaling. Proc Natl Acad Sci U S A 98:13884–13888

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Krueger A, Schmitz I, Baumann S, Krammer P, Kirchhoff S (2001) Cellular flice-inhibitory protein splice variants inhibit different steps of caspase-8 activation at the CD95 death inducing signaling complex. J Biol Chem 276:20633–20640

    CAS  PubMed  Google Scholar 

  45. Jin Z, Mcdonald IE, Dicker D, El-Deiry W (2004) Deficient tumor necrosis factor-related apoptosis-inducing ligand (Trail) death receptor transport to the cell surface in human colon cancer cells selected for resistance to trail-induced apoptosis. J Biol Chem 279:35829–35839

    CAS  PubMed  Google Scholar 

  46. Yeh W, Itie A, Elia A, Ng M, Shu H, Wakeham A, Mirtsos C, Suzuki N, Bonnard M, Goeddel D, Mak T (2000) Requirement for casper (C-Flip) in regulation of death receptor-induced apoptosis and embryonic development. Immunity 12:633–642

    CAS  PubMed  Google Scholar 

  47. Chang D, Xing Z, Pan Y, Algeciras-Schimnich A, Barnhart B, Yaish-Ohad S, Peter M, Yang X (2002) c-FLIPL is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis. EMBO J 21:3704–3714

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Micheau O, Thome M, Schneider P, Holler N, Tschopp J, Nicholson DW, Briand C, Grutter M (2002) The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex. J Biol Chem 277:45162–45171

    CAS  PubMed  Google Scholar 

  49. Boatright K, Deis C, Denault J-B, Sutherlin D, Salvesen G (2004) Activation of caspases-8 and -10 by FLIPL. Biochem J 382:651–657

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Chen G, Goeddel DV (2002) TNF-R1 signaling: a beautiful pathway. Science 296:1634–1635

    CAS  PubMed  Google Scholar 

  51. Wang E, Marcotte R, Petroulakis E (1999) Signaling pathway for apoptosis: a racetrack for life or death. J Cell Biochem Suppl 32–33:95–102

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  53. Stanger B, Leder P, Lee T, Kim E, Seed B (1995) RIP: a novel protein containing a death domain that interacts with FAS/Apo-1 (CD95) in yeast and causes cell death. Cell 81:513–523

    CAS  PubMed  Google Scholar 

  54. Pitti R, Marsters S, Ruppert S, Donahue C, Moore A, Ashkenaz IA (1996) Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 271:12687–12690

    CAS  PubMed  Google Scholar 

  55. Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3:673–682

    CAS  PubMed  Google Scholar 

  56. Thomas WD, Hersey P (1998) TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in Fas ligand-resistant melanoma cells and mediates CD4 T cell killing of target cells. J Immunol 161:2195–2200

    CAS  PubMed  Google Scholar 

  57. Smyth MJ, Cretney E, Takeda K, Wiltrout RH, Sedger LM, Kayagaki N, Yagita H, Okumura K (2001) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis. J Exp Med 193:661–670

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Takeda K, Hayakawa Y, Smyth MJ, Kayagaki N, Yamaguchi N, Kakuta S, Iwakura Y, Yagita H, Okumura K (2001) Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nat Med 7:94–100

    CAS  PubMed  Google Scholar 

  59. Cretney E, Takeda K, Yagita H, Glaccum M, Peschon JJ, Smyth MJ (2002) Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice. J Immunol 168:1356–1361

    CAS  PubMed  Google Scholar 

  60. Pan G, O’Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (1997) The receptor for the cytotoxic ligand TRAIL. Science 276:111–113

    CAS  PubMed  Google Scholar 

  61. Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT (1997) TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 16:5386–5397

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Wu GS, Burns TF, McDonald ER 3rd, Jiang W, Meng R, Krantz ID, Kao G, Gan DD, Zhou JY, Muschel R, Hamilton SR, Spinner NB, Markowitz S, Wu G, el-Deiry WS (1997) KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat Genet 17:141–143

    CAS  PubMed  Google Scholar 

  63. Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277:818–821

    CAS  PubMed  Google Scholar 

  64. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM (1997) An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277:815–818

    CAS  PubMed  Google Scholar 

  65. Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR (1998) Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273:14363–14367

    CAS  PubMed  Google Scholar 

  66. Ashkenazi A (2002) Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2:420–430

    CAS  PubMed  Google Scholar 

  67. Wagner KW, Punnoose EA, Januario T, Lawrence DA, Pitti RM, Lancaster K, Lee D, von Goetz M, Yee SF, Totpal K, Huw L, Katta V, Cavet G, Hymowitz SG, Amler L, Ashkenazi A (2007) Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med 13:1070–1077

    CAS  PubMed  Google Scholar 

  68. Deng Y, Lin Y, Wu X (2002) TRAIL-induced apoptosis requires Bax-dependent mitochondrial release of Smac/DIABLO. Genes Dev 16:33–45

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Verhagen AM, Silke J, Ekert PG, Pakusch M, Kaufmann H, Connolly LM, Day CL, Tikoo A, Burke R, Wrobel C, Moritz RL, Simpson RJ, Vaux DL (2002) HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J Biol Chem 277:445–454

    CAS  PubMed  Google Scholar 

  70. Cook AL, Frydenberg M, Haynes JM (2002) Protein kinase G activation of K(ATP) channels in human-cultured prostatic stromal cells. Cell Signal 14:1023–1029

    CAS  PubMed  Google Scholar 

  71. Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, DeForge L, Koumenis IL, Lewis D, Harris L, Bussiere J, Koeppen H, Shahrokh Z, Schwall RH (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104:155–162

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Zhang XD, Franco A, Myers K, Gray C, Nguyen T, Hersey P (1999) Relation of TNF-related apoptosis-inducing ligand (TRAIL) receptor and FLICE-inhibitory protein expression to TRAIL-induced apoptosis of melanoma. Cancer Res 59:2747–2753

    CAS  PubMed  Google Scholar 

  73. Kim JH, Ajaz M, Lokshin A, Lee YJ (2003) Role of antiapoptotic proteins in tumor necrosis factor-related apoptosis-inducing ligand and cisplatin-augmented apoptosis. Clin Cancer Res 9:3134–3141

    CAS  PubMed  Google Scholar 

  74. Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, Harran PG (2004) A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science 305:1471–1474

    CAS  PubMed  Google Scholar 

  75. Shankar S, Srivastava RK (2004) Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications. Drug Resist Updat 7:139–156

    CAS  PubMed  Google Scholar 

  76. Kroemer G (2003) Mitochondrial control of apoptosis: an introduction. Biochem Biophys Res Commun 304:433–435

    CAS  PubMed  Google Scholar 

  77. Fesik SW (2000) Insights into programmed cell death through structural biology. Cell 103:273–282

    CAS  PubMed  Google Scholar 

  78. Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776

    CAS  PubMed  Google Scholar 

  79. Zong WX, Lindsten T, Ross AJ, MacGregor GR, Thompson CB (2001) BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev 15:1481–1486

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, Korsmeyer SJ (2001) BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell 8:705–711

    CAS  PubMed  Google Scholar 

  81. Schuler M, Green DR (2001) Mechanisms of p53-dependent apoptosis. Biochem Soc Trans 29:684–688

    CAS  PubMed  Google Scholar 

  82. Chipuk JE, Green DR (2003) p53’s believe it or not: lessons on transcription-independent death. J Clin Immunol 23:355–361

    CAS  PubMed  Google Scholar 

  83. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91:231–241

    CAS  PubMed  Google Scholar 

  84. Li H, Zhu H, Xu CJ, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491–501

    CAS  PubMed  Google Scholar 

  85. Luo X, Budihardjo I, Zou H, Slaughter C, Wang X (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94:481–490

    CAS  PubMed  Google Scholar 

  86. Zamzami N, Marchetti P, Castedo M, Hirsch T, Susin SA, Masse B, Kroemer G (1996) Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis. FEBS Lett 384:53–57

    CAS  PubMed  Google Scholar 

  87. Waring P, Beaver J (1996) Cyclosporin A rescues thymocytes from apoptosis induced by very low concentrations of thapsigargin: effects on mitochondrial function. Exp Cell Res 227:264–276

    CAS  PubMed  Google Scholar 

  88. Scarlett JL, Murphy MP (1997) Release of apoptogenic proteins from the mitochondrial intermembrane space during the mitochondrial permeability transition. FEBS Lett 418:282–286

    CAS  PubMed  Google Scholar 

  89. Ghiotto F, Fais F, Bruno S (2010) BH3-only proteins: the death-puppeteer’s wires. Cytometry A 77:11–21

    PubMed  Google Scholar 

  90. De Giorgi F, Lartigue L, Bauer MK, Schubert A, Grimm S, Hanson GT, Remington SJ, Youle RJ, Ichas F (2002) The permeability transition pore signals apoptosis by directing Bax translocation and multimerization. FASEB J 16:607–609

    PubMed  Google Scholar 

  91. Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11:621–632

    CAS  PubMed  Google Scholar 

  92. Eskes R, Desagher S, Antonsson B, Martinou JC (2000) Bid induces the oligomerization and insertion of Bax into the outer mitochondrial membrane. Mol Cell Biol 20:929–935

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A, Ashiya M, Thompson CB, Korsmeyer SJ (2000) tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev 14:2060–2071

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Hsu YT, Wolter KG, Youle RJ (1997) Cytosol-to-membrane redistribution of Bax and Bcl-X(L) during apoptosis. Proc Natl Acad Sci U S A 94:3668–3672

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Lovell JF, Billen LP, Bindner S, Shamas-Din A, Fradin C, Leber B, Andrews DW (2008) Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax. Cell 135:1074–1084

    CAS  PubMed  Google Scholar 

  96. George NM, Evans JJ, Luo X (2007) A three-helix homo-oligomerization domain containing BH3 and BH1 is responsible for the apoptotic activity of Bax. Genes Dev 21:1937–1948

    CAS  PubMed Central  PubMed  Google Scholar 

  97. Dewson G, Kratina T, Sim HW, Puthalakath H, Adams JM, Colman PM, Kluck RM (2008) To trigger apoptosis, Bak exposes its BH3 domain and homodimerizes via BH3: groove interactions. Mol Cell 30:369–380

    CAS  PubMed  Google Scholar 

  98. Dewson G, Kratina T, Czabotar P, Day CL, Adams JM, Kluck RM (2009) Bak activation for apoptosis involves oligomerization of dimers via their alpha6 helices. Mol Cell 36:696–703

    CAS  PubMed  Google Scholar 

  99. Saito M, Korsmeyer SJ, Schlesinger PH (2000) BAX-dependent transport of cytochrome c reconstituted in pure liposomes. Nat Cell Biol 2:553–555

    CAS  PubMed  Google Scholar 

  100. Nechushtan A, Smith CL, Lamensdorf I, Yoon SH, Youle RJ (2001) Bax and Bak coalesce into novel mitochondria-associated clusters during apoptosis. J Cell Biol 153:1265–1276

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Zhou L, Chang DC (2008) Dynamics and structure of the Bax-Bak complex responsible for releasing mitochondrial proteins during apoptosis. J Cell Sci 121:2186–2196

    CAS  PubMed  Google Scholar 

  102. Goldstein JC, Waterhouse NJ, Juin P, Evan GI, Green DR (2000) The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant. Nat Cell Biol 2:156–162

    CAS  PubMed  Google Scholar 

  103. Muchmore SW, Sattler M, Liang H, Meadows RP, Harlan JE, Yoon HS, Nettesheim D, Chang BS, Thompson CB, Wong SL, Ng SL, Fesik SW (1996) X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 381:335–341

    CAS  PubMed  Google Scholar 

  104. Suzuki M, Youle RJ, Tjandra N (2000) Structure of Bax: coregulation of dimer formation and intracellular localization. Cell 103:645–654

    CAS  PubMed  Google Scholar 

  105. Martinez-Caballero S, Dejean LM, Kinnally MS, Oh KJ, Mannella CA, Kinnally KW (2009) Assembly of the mitochondrial apoptosis-induced channel, MAC. J Biol Chem 284:12235–12245

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Basanez G, Nechushtan A, Drozhinin O, Chanturiya A, Choe E, Tutt S, Wood KA, Hsu Y, Zimmerberg J, Youle RJ (1999) Bax, but not Bcl-xL, decreases the lifetime of planar phospholipid bilayer membranes at subnanomolar concentrations. Proc Natl Acad Sci U S A 96:5492–5497

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Basanez G, Sharpe JC, Galanis J, Brandt TB, Hardwick JM, Zimmerberg J (2002) Bax-type apoptotic proteins porate pure lipid bilayers through a mechanism sensitive to intrinsic monolayer curvature. J Biol Chem 277:49360–49365

    CAS  PubMed  Google Scholar 

  108. Hardwick JM, Polster BM (2002) Bax, along with lipid conspirators, allows cytochrome c to escape mitochondria. Mol Cell 10:963–965

    CAS  PubMed  Google Scholar 

  109. Polster BM, Basanez G, Etxebarria A, Hardwick JM, Nicholls DG (2005) Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. J Biol Chem 280:6447–6454

    CAS  PubMed  Google Scholar 

  110. Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CY, Sasaki T, Elia AJ, Cheng HY, Ravagnan L, Ferri KF, Zamzami N, Wakeham A, Hakem R, Yoshida H, Kong YY, Mak TW, Zuniga-Pflucker JC, Kroemer G, Penninger JM (2001) Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature 410:549–554

    CAS  PubMed  Google Scholar 

  111. Cipolat S, Rudka T, Hartmann D, Costa V, Serneels L, Craessaerts K, Metzger K, Frezza C, Annaert W, D’Adamio L, Derks C, Dejaegere T, Pellegrini L, D’Hooge R, Scorrano L, De Strooper B (2006) Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell 126:163–175

    CAS  PubMed  Google Scholar 

  112. Frezza C, Cipolat S, Martins de Brito O, Micaroni M, Beznoussenko GV, Rudka T, Bartoli D, Polishuck RS, Danial NN, De Strooper B, Scorrano L (2006) OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 126:177–189

    CAS  PubMed  Google Scholar 

  113. Monian P, Jiang X (2012) Clearing the final hurdles to mitochondrial apoptosis: regulation post cytochrome C release. Exp Oncol 34:185–191

    CAS  PubMed  Google Scholar 

  114. Yuan S, Akey CW (2013) Apoptosome structure, assembly, and procaspase activation. Structure 21:501–515

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Szabo I, Zoratti M (1993) The mitochondrial permeability transition pore may comprise VDAC molecules. I. Binary structure and voltage dependence of the pore. FEBS Lett 330:201–205

    CAS  PubMed  Google Scholar 

  116. Neer EJ, Schmidt CJ, Nambudripad R, Smith TF (1994) The ancient regulatory-protein family of WD-repeat proteins. Nature 371:297–300

    CAS  PubMed  Google Scholar 

  117. Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X, Akey CW (2002) Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol Cell 9:423–432

    CAS  PubMed  Google Scholar 

  118. Zou H, Li Y, Liu X, Wang X (1999) An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 274:11549–11556

    CAS  PubMed  Google Scholar 

  119. Shi Y (2002) Apoptosome: the cellular engine for the activation of caspase-9. Structure 10:285–288

    CAS  PubMed  Google Scholar 

  120. Reubold TF, Eschenburg S (2012) A molecular view on signal transduction by the apoptosome. Cell Signal 24:1420–1425

    CAS  PubMed  Google Scholar 

  121. Riedl SJ, Salvesen GS (2007) The apoptosome: signalling platform of cell death. Nat Rev Mol Cell Biol 8:405–413

    CAS  PubMed  Google Scholar 

  122. Yuan S, Yu X, Asara JM, Heuser JE, Ludtke SJ, Akey CW (2011) The holo-apoptosome: activation of procaspase-9 and interactions with caspase-3. Structure 19:1084–1096

    CAS  PubMed Central  PubMed  Google Scholar 

  123. Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102:33–42

    CAS  PubMed  Google Scholar 

  124. Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R (2001) A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell 8:613–621

    CAS  PubMed  Google Scholar 

  125. Hegde R, Srinivasula SM, Datta P, Madesh M, Wassell R, Zhang Z, Cheong N, Nejmeh J, Fernandes-Alnemri T, Hoshino S, Alnemri ES (2003) The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein. J Biol Chem 278:38699–38706

    CAS  PubMed  Google Scholar 

  126. Xiao R, Gao Y, Shen Q, Li C, Chang W, Chai B (2013) Polypeptide chain release factor eRF3 is a novel molecular partner of survivin. Cell Biol Int 37(4):359–369

    CAS  PubMed  Google Scholar 

  127. Li LY, Luo X, Wang X (2001) Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95–99

    CAS  PubMed  Google Scholar 

  128. Jensen LE, Bultynck G, Luyten T, Amijee H, Bootman MD, Roderick HL (2013) Alzheimer’s disease-associated peptide Abeta42 mobilizes ER Ca(2+) via InsP3R-dependent and -independent mechanisms. Front Mol Neurosci 6:36

    PubMed Central  PubMed  Google Scholar 

  129. Rao RV, Ellerby HM, Bredesen DE (2004) Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ 11:372–380

    CAS  PubMed  Google Scholar 

  130. Wojcik C, Rowicka M, Kudlicki A, Nowis D, McConnell E, Kujawa M, DeMartino GN (2006) Valosin-containing protein (p97) is a regulator of endoplasmic reticulum stress and of the degradation of N-end rule and ubiquitin-fusion degradation pathway substrates in mammalian cells. Mol Biol Cell 17:4606–4618

    CAS  PubMed Central  PubMed  Google Scholar 

  131. Groenendyk J, Michalak M (2005) Endoplasmic reticulum quality control and apoptosis. Acta Biochim Pol 52:381–395

    CAS  PubMed  Google Scholar 

  132. Grimm S (2012) The ER-mitochondria interface: the social network of cell death. Biochim Biophys Acta 1823:327–334

    CAS  PubMed  Google Scholar 

  133. Szegezdi E, Fitzgerald U, Samali A (2003) Caspase-12 and ER-stress-mediated apoptosis: the story so far. Ann N Y Acad Sci 1010:186–194

    CAS  PubMed  Google Scholar 

  134. Verkhratsky A, Toescu EC (2003) Endoplasmic reticulum Ca(2+) homeostasis and neuronal death. J Cell Mol Med 7:351–361

    CAS  PubMed  Google Scholar 

  135. Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9:231–241

    CAS  PubMed  Google Scholar 

  136. Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH, Peter ME (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17:1675–1687

    CAS  PubMed Central  PubMed  Google Scholar 

  137. Bennett M, Macdonald K, Chan SW, Luzio JP, Simari R, Weissberg P (1998) Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis. Science 282:290–293

    CAS  PubMed  Google Scholar 

  138. Kasibhatla S, Brunner T, Genestier L, Echeverri F, Mahboubi A, Green DR (1998) DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-kappa B and AP-1. Mol Cell 1:543–551

    CAS  PubMed  Google Scholar 

  139. Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11:700–714

    CAS  PubMed  Google Scholar 

  140. Tait SW, Green DR (2008) Caspase-independent cell death: leaving the set without the final cut. Oncogene 27:6452–6461

    CAS  PubMed Central  PubMed  Google Scholar 

  141. Ellis HM, Horvitz HR (1986) Genetic control of programmed cell death in the nematode C. elegans. Cell 44:817–829

    CAS  PubMed  Google Scholar 

  142. Huh JR, Foe I, Muro I, Chen CH, Seol JH, Yoo SJ, Guo M, Park JM, Hay BA (2007) The Drosophila inhibitor of apoptosis (IAP) DIAP2 is dispensable for cell survival, required for the innate immune response to gram-negative bacterial infection, and can be negatively regulated by the reaper/hid/grim family of IAP-binding apoptosis inducers. J Biol Chem 282:2056–2068

    CAS  PubMed  Google Scholar 

  143. Haraguchi M, Torii S, Matsuzawa S, Xie Z, Kitada S, Krajewski S, Yoshida H, Mak TW, Reed JC (2000) Apoptotic protease activating factor 1 (Apaf-1)-independent cell death suppression by Bcl-2. J Exp Med 191:1709–1720

    CAS  PubMed Central  PubMed  Google Scholar 

  144. Lindsten T, Ross AJ, King A, Zong WX, Rathmell JC, Shiels HA, Ulrich E, Waymire KG, Mahar P, Frauwirth K, Chen Y, Wei M, Eng VM, Adelman DM, Simon MC, Ma A, Golden JA, Evan G, Korsmeyer SJ, MacGregor GR, Thompson CB (2000) The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell 6:1389–1399

    CAS  PubMed Central  PubMed  Google Scholar 

  145. Cecconi F, Alvarez-Bolado G, Meyer BI, Roth KA, Gruss P (1998) Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. Cell 94:727–737

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  147. Hao Z, Duncan GS, Chang CC, Elia A, Fang M, Wakeham A, Okada H, Calzascia T, Jang Y, You-Ten A, Yeh WC, Ohashi P, Wang X, Mak TW (2005) Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis. Cell 121:579–591

    CAS  PubMed  Google Scholar 

  148. Chipuk JE, Green DR (2005) Do inducers of apoptosis trigger caspase-independent cell death? Nat Rev Mol Cell Biol 6:268–275

    CAS  PubMed  Google Scholar 

  149. Johnson CE, Huang YY, Parrish AB, Smith MI, Vaughn AE, Zhang Q, Wright KM, Van Dyke T, Wechsler-Reya RJ, Kornbluth S, Deshmukh M (2007) Differential Apaf-1 levels allow cytochrome c to induce apoptosis in brain tumors but not in normal neural tissues. Proc Natl Acad Sci U S A 104:20820–20825

    CAS  PubMed Central  PubMed  Google Scholar 

  150. Sanchis D, Mayorga M, Ballester M, Comella JX (2003) Lack of Apaf-1 expression confers resistance to cytochrome c-driven apoptosis in cardiomyocytes. Cell Death Differ 10:977–986

    CAS  PubMed  Google Scholar 

  151. Goldstein JC, Kluck RM, Green DR (2000) A single cell analysis of apoptosis. Ordering the apoptotic phenotype. Ann N Y Acad Sci 926:132–141

    CAS  PubMed  Google Scholar 

  152. Cauwels A, Janssen B, Waeytens A, Cuvelier C, Brouckaert P (2003) Caspase inhibition causes hyperacute tumor necrosis factor-induced shock via oxidative stress and phospholipase A2. Nat Immunol 4:387–393

    CAS  PubMed  Google Scholar 

  153. Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B, Tschopp J (2000) Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 1:489–495

    CAS  PubMed  Google Scholar 

  154. Temkin V, Huang Q, Liu H, Osada H, Pope RM (2006) Inhibition of ADP/ATP exchange in receptor-interacting protein-mediated necrosis. Mol Cell Biol 26:2215–2225

    CAS  PubMed Central  PubMed  Google Scholar 

  155. Ricci JE, Munoz-Pinedo C, Fitzgerald P, Bailly-Maitre B, Perkins GA, Yadava N, Scheffler IE, Ellisman MH, Green DR (2004) Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain. Cell 117:773–786

    CAS  PubMed  Google Scholar 

  156. Colell A, Ricci JE, Tait S, Milasta S, Maurer U, Bouchier-Hayes L, Fitzgerald P, Guio-Carrion A, Waterhouse NJ, Li CW, Mari B, Barbry P, Newmeyer DD, Beere HM, Green DR (2007) GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell 129:983–997

    CAS  PubMed  Google Scholar 

  157. Gasser SM, Daum G, Schatz G (1982) Import of proteins into mitochondria. Energy-dependent uptake of precursors by isolated mitochondria. J Biol Chem 257:13034–13041

    CAS  PubMed  Google Scholar 

  158. Ewen CL, Kane KP, Bleackley RC (2012) A quarter century of granzymes. Cell Death Differ 19:28–35

    CAS  PubMed Central  PubMed  Google Scholar 

  159. Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 4:552–565

    CAS  PubMed  Google Scholar 

  160. Odake S, Kam CM, Narasimhan L, Poe M, Blake JT, Krahenbuhl O, Tschopp J, Powers JC (1991) Human and murine cytotoxic T lymphocyte serine proteases: subsite mapping with peptide thioester substrates and inhibition of enzyme activity and cytolysis by isocoumarins. Biochemistry 30:2217–2227

    CAS  PubMed  Google Scholar 

  161. Adrain C, Murphy BM, Martin SJ (2005) Molecular ordering of the caspase activation cascade initiated by the cytotoxic T lymphocyte/natural killer (CTL/NK) protease granzyme B. J Biol Chem 280:4663–4673

    CAS  PubMed  Google Scholar 

  162. Andrade F, Roy S, Nicholson D, Thornberry N, Rosen A, Casciola-Rosen L (1998) Granzyme B directly and efficiently cleaves several downstream caspase substrates: implications for CTL-induced apoptosis. Immunity 8:451–460

    CAS  PubMed  Google Scholar 

  163. Darmon AJ, Nicholson DW, Bleackley RC (1995) Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B. Nature 377:446–448

    CAS  PubMed  Google Scholar 

  164. Martin SJ, Amarante-Mendes GP, Shi L, Chuang TH, Casiano CA, O’Brien GA, Fitzgerald P, Tan EM, Bokoch GM, Greenberg AH, Green DR (1996) The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism. EMBO J 15:2407–2416

    CAS  PubMed Central  PubMed  Google Scholar 

  165. Medema JP, Toes RE, Scaffidi C, Zheng TS, Flavell RA, Melief CJ, Peter ME, Offringa R, Krammer PH (1997) Cleavage of FLICE (caspase-8) by granzyme B during cytotoxic T lymphocyte-induced apoptosis. Eur J Immunol 27:3492–3498

    CAS  PubMed  Google Scholar 

  166. Van de Craen M, Van den Brande I, Declercq W, Irmler M, Beyaert R, Tschopp J, Fiers W, Vandenabeele P (1997) Cleavage of caspase family members by granzyme B: a comparative study in vitro. Eur J Immunol 27:1296–1299

    PubMed  Google Scholar 

  167. Atkinson EA, Barry M, Darmon AJ, Shostak I, Turner PC, Moyer RW, Bleackley RC (1998) Cytotoxic T lymphocyte-assisted suicide. Caspase 3 activation is primarily the result of the direct action of granzyme B. J Biol Chem 273:21261–21266

    CAS  PubMed  Google Scholar 

  168. Darmon AJ, Ley TJ, Nicholson DW, Bleackley RC (1996) Cleavage of CPP32 by granzyme B represents a critical role for granzyme B in the induction of target cell DNA fragmentation. J Biol Chem 271:21709–21712

    CAS  PubMed  Google Scholar 

  169. Sorimachi H, Ishiura S, Suzuki K (1997) Structure and physiological function of calpains. Biochem J 328(Pt 3):721–732

    CAS  PubMed Central  PubMed  Google Scholar 

  170. Ray SK, Hogan EL, Banik NL (2003) Calpain in the pathophysiology of spinal cord injury: neuroprotection with calpain inhibitors. Brain Res Brain Res Rev 42:169–185

    CAS  PubMed  Google Scholar 

  171. Saido TC, Sorimachi H, Suzuki K (1994) Calpain: new perspectives in molecular diversity and physiological-pathological involvement. FASEB J 8:814–822

    CAS  PubMed  Google Scholar 

  172. Stys PK, Jiang Q (2002) Calpain-dependent neurofilament breakdown in anoxic and ischemic rat central axons. Neurosci Lett 328:150–154

    CAS  PubMed  Google Scholar 

  173. Santella L, Carafoli E (1997) Calcium signaling in the cell nucleus. FASEB J 11:1091–1109

    CAS  PubMed  Google Scholar 

  174. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    CAS  PubMed Central  PubMed  Google Scholar 

  175. Vande Walle L, Lamkanfi M, Vandenabeele P (2008) The mitochondrial serine protease HtrA2/Omi: an overview. Cell Death Differ 15:453–460

    CAS  PubMed  Google Scholar 

  176. Sheikh MS, Fornace AJ Jr (2000) Death and decoy receptors and p53-mediated apoptosis. Leukemia 14:1509–1513

    CAS  PubMed  Google Scholar 

  177. Goyal L (2001) Cell death inhibition: keeping caspases in check. Cell 104:805–808

    CAS  PubMed  Google Scholar 

  178. White MK, McCubrey JA (2001) Suppression of apoptosis: role in cell growth and neoplasia. Leukemia 15:1011–1021

    CAS  PubMed  Google Scholar 

  179. Vila M, Przedborski S (2003) Targeting programmed cell death in neurodegenerative diseases. Nat Rev Neurosci 4:365–375

    CAS  PubMed  Google Scholar 

  180. Lev N, Melamed E, Offen D (2003) Apoptosis and Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry 27:245–250

    CAS  PubMed  Google Scholar 

  181. Jellinger KA (2001) Cell death mechanisms in neurodegeneration. J Cell Mol Med 5:1–17

    CAS  PubMed  Google Scholar 

  182. Ameisen JC (1992) The programmed cell death theory of AIDS pathogenesis: implications, testable predictions, and confrontation with experimental findings. Immunodefic Rev 3:237–246

    CAS  PubMed  Google Scholar 

  183. Copeland KF, Heeney JL (1996) T helper cell activation and human retroviral pathogenesis. Microbiol Rev 60:722–742

    CAS  PubMed Central  PubMed  Google Scholar 

  184. Bush JA, Li G (2002) Cancer chemoresistance: the relationship between p53 and multidrug transporters. Int J Cancer 98:323–330

    CAS  PubMed  Google Scholar 

  185. Nielsen LL, Maneval DC (1998) P53 tumor suppressor gene therapy for cancer. Cancer Gene Ther 5:52–63

    CAS  PubMed  Google Scholar 

  186. Zhan M, Yu D, Lang A, Li L, Pollock RE (2001) Wild type p53 sensitizes soft tissue sarcoma cells to doxorubicin by down-regulating multidrug resistance-1 expression. Cancer 92:1556–1566

    CAS  PubMed  Google Scholar 

  187. Maccioni RB, Munoz JP, Barbeito L (2001) The molecular bases of Alzheimer’s disease and other neurodegenerative disorders. Arch Med Res 32:367–381

    CAS  PubMed  Google Scholar 

  188. Butterfield DA, Bader Lange ML, Sultana R (2010) Involvements of the lipid peroxidation product, HNE, in the pathogenesis and progression of Alzheimer’s disease. Biochim Biophys Acta 1801:924–929

    CAS  PubMed Central  PubMed  Google Scholar 

  189. Battaglia F, Trinchese F, Liu S, Walter S, Nixon RA, Arancio O (2003) Calpain inhibitors, a treatment for Alzheimer’s disease: position paper. J Mol Neurosci 20:357–362

    CAS  PubMed  Google Scholar 

  190. Boland B, Campbell V (2003) beta-Amyloid (1-40)-induced apoptosis of cultured cortical neurones involves calpain-mediated cleavage of poly-ADP-ribose polymerase. Neurobiol Aging 24:179–186

    CAS  PubMed  Google Scholar 

  191. Fischer U, Schulze-Osthoff K (2005) New approaches and therapeutics targeting apoptosis in disease. Pharmacol Rev 57:187–215

    CAS  PubMed  Google Scholar 

  192. Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163

    CAS  PubMed  Google Scholar 

  193. Galluzzi L, Vitale I, Kepp O, Seror C, Hangen E, Perfettini JL, Modjtahedi N, Kroemer G (2008) Methods to dissect mitochondrial membrane permeabilization in the course of apoptosis. Methods Enzymol 442:355–374

    PubMed  Google Scholar 

  194. Hisatomi T, Ishibashi T, Miller JW, Kroemer G (2009) Pharmacological inhibition of mitochondrial membrane permeabilization for neuroprotection. Exp Neurol 218:347–352

    CAS  PubMed  Google Scholar 

  195. Siman R, Card JP, Davis LG (1990) Proteolytic processing of beta-amyloid precursor by calpain I. J Neurosci 10:2400–2411

    CAS  PubMed  Google Scholar 

  196. Samantaray S, Ray SK, Banik NL (2008) Calpain as a potential therapeutic target in Parkinson’s disease. CNS Neurol Disord Drug Targets 7:305–312

    CAS  PubMed  Google Scholar 

  197. Camins A, Crespo-Biel N, Junyent F, Verdaguer E, Canudas AM, Pallas M (2009) Calpains as a target for therapy of neurodegenerative diseases: putative role of lithium. Curr Drug Metab 10:433–447

    CAS  PubMed  Google Scholar 

  198. Scholzke MN, Potrovita I, Subramaniam S, Prinz S, Schwaninger M (2003) Glutamate activates NF-kappaB through calpain in neurons. Eur J Neurosci 18:3305–3310

    PubMed  Google Scholar 

  199. Lopes JP, Oliveira CR, Agostinho P (2010) Neurodegeneration in an Abeta-induced model of Alzheimer’s disease: the role of Cdk5. Aging Cell 9:64–77

    CAS  PubMed  Google Scholar 

  200. Rami A (2003) Ischemic neuronal death in the rat hippocampus: the calpain-calpastatin-caspase hypothesis. Neurobiol Dis 13:75–88

    CAS  PubMed  Google Scholar 

  201. Wilcock GK (2003) Memantine for the treatment of dementia. Lancet Neurol 2:503–505

    CAS  PubMed  Google Scholar 

  202. Molinuevo JL, Llado A, Rami L (2005) Memantine: targeting glutamate excitotoxicity in Alzheimer’s disease and other dementias. Am J Alzheimers Dis Other Demen 20:77–85

    PubMed  Google Scholar 

  203. Goni-Oliver P, Avila J, Hernandez F (2009) Memantine inhibits calpain-mediated truncation of GSK-3 induced by NMDA: implications in Alzheimer’s disease. J Alzheimers Dis 18:843–848

    CAS  PubMed  Google Scholar 

  204. Xie X, Zhao X, Liu Y, Zhang J, Matusik RJ, Slawin KM, Spencer DM (2001) Adenovirus-mediated tissue-targeted expression of a caspase-9-based artificial death switch for the treatment of prostate cancer. Cancer Res 61:6795–6804

    CAS  PubMed  Google Scholar 

  205. Komata T, Kondo Y, Kanzawa T, Hirohata S, Koga S, Sumiyoshi H, Srinivasula SM, Barna BP, Germano IM, Takakura M, Inoue M, Alnemri ES, Shay JW, Kyo S, Kondo S (2001) Treatment of malignant glioma cells with the transfer of constitutively active caspase-6 using the human telomerase catalytic subunit (human telomerase reverse transcriptase) gene promoter. Cancer Res 61:5796–5802

    CAS  PubMed  Google Scholar 

  206. Jia LT, Zhang LH, Yu CJ, Zhao J, Xu YM, Gui JH, Jin M, Ji ZL, Wen WH, Wang CJ, Chen SY, Yang AG (2003) Specific tumoricidal activity of a secreted proapoptotic protein consisting of HER2 antibody and constitutively active caspase-3. Cancer Res 63:3257–3262

    CAS  PubMed  Google Scholar 

  207. Xu YM, Wang LF, Jia LT, Qiu XC, Zhao J, Yu CJ, Zhang R, Zhu F, Wang CJ, Jin BQ, Chen SY, Yang AG (2004) A caspase-6 and anti-human epidermal growth factor receptor-2 (HER2) antibody chimeric molecule suppresses the growth of HER2-overexpressing tumors. J Immunol 173:61–67

    CAS  PubMed  Google Scholar 

  208. Buckley CD, Pilling D, Henriquez NV, Parsonage G, Threlfall K, Scheel-Toellner D, Simmons DL, Akbar AN, Lord JM, Salmon M (1999) RGD peptides induce apoptosis by direct caspase-3 activation. Nature 397:534–539

    CAS  PubMed  Google Scholar 

  209. Skorko-Glonek J, Zurawa-Janicka D, Koper T, Jarzab M, Figaj D, Glaza P, Lipinska B (2013) HtrA protease family as therapeutic targets. Curr Pharm Des 19:977–1009

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Integrated Biophysics and Structural Biology Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, 410210, India

    Nitu Singh & Kakoli Bose

Authors
  1. Nitu Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kakoli Bose
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kakoli Bose .

Editor information

Editors and Affiliations

  1. Tata Memorial Centre, Integrated Biophysics and Structural Biology Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Navi Mumbai, India

    Kakoli Bose

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Singh, N., Bose, K. (2015). Apoptosis: Pathways, Molecules and Beyond. In: Bose, K. (eds) Proteases in Apoptosis: Pathways, Protocols and Translational Advances. Springer, Cham. https://doi.org/10.1007/978-3-319-19497-4_1

Download citation

Publish with us

Policies and ethics

Search

Navigation