The molecular machinery regulating apoptosis signal transduction and its implication in human physiology and pathophysiologies

Current Molecular Medicine

Volumn 11, Issue 1, 2011, Pages 31-47

  Hellwig, C T ^a   Passante, E ^a   Rehm, M ^a  

^a ROYAL COLLEGE OF SURGEONS IN IRELAND   (Ireland)

Author keywords

Apoptosis; Bcl 2 protein family; Cancer; Caspases; Cell death; Death receptors; Inhibitor of apoptosis proteins; Mitochondrial outer membrane permeabilisation

Indexed keywords

CASPASE; PROTEIN BCL 2;

APOPTOSIS; ARTICLE; CANCER CLASSIFICATION; CANCER GROWTH; CELL FATE; ENZYME ACTIVATION; HUMAN; MEDICAL RESEARCH; MITOCHONDRIAL MEMBRANE; OLIGOMERIZATION; PROTEIN BINDING; PROTEIN MOTIF; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; ANIMALS; APOPTOSIS; CASPASES; CELL MEMBRANE PERMEABILITY; DIABETES MELLITUS; HUMANS; INHIBITOR OF APOPTOSIS PROTEINS; MITOCHONDRIAL MEMBRANES; NEOPLASMS; PROTO-ONCOGENE PROTEINS C-BCL-2; RECEPTORS, DEATH DOMAIN;

EID: 79551663808     PISSN: 15665240     EISSN: None     Source Type: Journal    
DOI: 10.2174/156652411794474400     Document Type: Article

References (247)

1. Vogt CC. Untersuchungen über die Entwicklungsgeschichteder Geburtshelferkröte (Alytes obstetricians). Solothurn: Juntund Gassmann 1842; pp. 130.
2. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biologicalphenomenon with wide-ranging implications in tissuekinetics. Br J Cancer 1972; 26 (4): 239-57.
3. Sulston JE, Horvitz HR. Post-embryonic cell lineages of thenematode, Caenorhabditis elegans. Dev Biol 1977; 56 (1): 110-56.
4. Horvitz HR, Sulston JE. Isolation and geneticcharacterization of cell-lineage mutants of the nematodeCaenorhabditis elegans. Genetics 1980; 96 (2): 435-54.
5. Savill J, Fadok V, Henson P, Haslett C. Phagocyterecognition of cells undergoing apoptosis. Immunol Today 1993; 14 (3): 131-6.
6. Fullard J, Kale A, Baker N. Clearance of apoptotic corpses. Apoptosis 2009; 14 (8): 1029-37.
7. Festjens N, Vanden Berghe T, Vandenabeele P. Necrosis, awell-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta 2006; 1757 (9-10): 1371-87.
8. Codogno P, Meijer AJ. Autophagy and signaling: their role incell survival and cell death. Cell Death Differ 2005; 12 Suppl2: 1509-18.
9. Feig C, Peter ME. How apoptosis got the immune system inshape. Eur J Immunol 2007; 37 Suppl 1: S61-70.
10. Yuan J, Yankner BA. Apoptosis in the nervous system. Nature 2000; 407 (6805): 802-9.
11. Kuida K, Zheng TS, Na S, et al. Decreased apoptosis in thebrain and premature lethality in CPP32-deficient mice. Nature 1996; 384 (6607): 368-72.
12. Kang TB, Ben-Moshe T, Varfolomeev EE, et al. Caspase-8serves both apoptotic and nonapoptotic roles. J Immunol 2004; 173 (5): 2976-84.
13. Hakem R, Hakem A, Duncan GS, et al. Differentialrequirement for caspase 9 in apoptotic pathways in vivo. Cell 1998; 94 (3): 339-52.
14. Tabibzadeh S. The signals and molecular pathways involvedin human menstruation, a unique process of tissuedestruction and remodelling. Mol Hum Reprod 1996; 2 (2): 77-92.
15. Wright KM, Deshmukh M. Restricting apoptosis forpostmitotic cell survival and its relevance to cancer. Cell Cycle 2006; 5 (15): 1616-20.
16. Salmena L, Lemmers B, Hakem A, et al. Essential role forcaspase 8 in T-cell homeostasis and T-cell-mediatedimmunity. Genes Dev 2003; 17 (7): 883-95.
17. Giovannetti A, Pierdominici M, Di Iorio A, et al. Apoptosis inthe homeostasis of the immune system and in humanimmune mediated diseases. Curr Pharm Des 2008; 14 (3): 253-68.
18. Defrance T. Mature B cells: apoptosis checkpoints. Transplantation 2005; 79 (3 Suppl): S4-7.
19. Chowdhury D, Lieberman J. Death by a thousand cuts:granzyme pathways of programmed cell death. Annu Rev Immunol 2008; 26: 389-420.
20. Martinvalet D, Dykxhoorn DM, Ferrini R, Lieberman J. Granzyme A cleaves a mitochondrial complex I protein toinitiate caspase-independent cell death. Cell 2008; 133 (4): 681-92.
21. Chipuk JE, Green DR. Dissecting p53-dependent apoptosis. Cell Death Differ 2006; 13 (6): 994-1002.
22. Teodoro JG, Branton PE. Regulation of p53-dependentapoptosis, transcriptional repression, and cell transformationby phosphorylation of the 55-kilodalton E1B protein of humanadenovirus type 5. J Virol 1997; 71 (5): 3620-7.
23. Westphal D, Ledgerwood EC, Hibma MH, Fleming SB, Whelan EM, Mercer AA. A novel Bcl-2-like inhibitor ofapoptosis is encoded by the parapoxvirus ORF virus. J Virol 2007; 81 (13): 7178-88.
24. Wang XW, Forrester K, Yeh H, Feitelson MA, Gu JR, Harris CC. Hepatitis B virus X protein inhibits p53 sequence-specificDNA binding, transcriptional activity, and association withtranscription factor ERCC3. Proc Natl Acad Sci USA 1994; 91 (6): 2230-4.
25. Bargonetti J, Reynisdottir I, Friedman PN, Prives C. Sitespecificbinding of wild-type p53 to cellular DNA is inhibitedby SV40 T antigen and mutant p53. Genes Dev 1992; 6 (10): 1886-98.
26. Yew PR, Liu X, Berk AJ. Adenovirus E1B oncoprotein tethersa transcriptional repression domain to p53. Genes Dev 1994; 8 (2): 190-202.
27. Dobner T, Horikoshi N, Rubenwolf S, Shenk T. Blockage byadenovirus E4orf6 of transcriptional activation by the p53tumor suppressor. Science 1996; 272 (5267): 1470-3.
28. Tewari M, Dixit VM. Fas- and tumor necrosis factor-inducedapoptosis is inhibited by the poxvirus crmA gene product. JBiol Chem 1995; 270 (7): 3255-60.
29. Clem RJ, Fechheimer M, Miller LK. Prevention of apoptosisby a baculovirus gene during infection of insect cells. Science 1991; 254 (5036): 1388-90.
30. Hay S, Kannourakis G. A time to kill: viral manipulation of thecell death program. J Gen Virol 2002; 83 (Pt 7): 1547-64.
31. Greinert R. Skin cancer: new markers for better prevention. Pathobiology 2009; 76 (2): 64-81.
32. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Nonsmallcell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008; 83 (5): 584-94.
33. Royds JA, Iacopetta B. p53 and disease: when the guardianangel fails. Cell Death Differ 2006; 13 (6): 1017-26.
34. zur Hausen H. Papillomaviruses causing cancer: evasionfrom host-cell control in early events in carcinogenesis. J Natl Cancer Inst 2000; 92 (9): 690-8.
35. Yuan JN, Chao Y, Lee WP, et al. Chemotherapy withetoposide, doxorubicin, cisplatin, 5-fluorouracil, andleucovorin for patients with advanced hepatocellularcarcinoma. Med Oncol 2008; 25 (2): 201-6.
36. Haddad R, Colevas AD, Tishler R, et al. Docetaxel, cisplatin, and 5-fluorouracil-based induction chemotherapy in patientswith locally advanced squamous cell carcinoma of the headand neck: the Dana Farber Cancer Institute experience. Cancer 2003; 97 (2): 412-8.
37. Hitt R, Lopez-Pousa A, Martinez-Trufero J, et al. Phase IIIstudy comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followedby chemoradiotherapy in locally advanced head and neckcancer. J Clin Oncol 2005; 23 (34): 8636-45.
38. Distler M, Ruckert F, Dittert DD, et al. Curative resection of aprimarily unresectable acinar cell carcinoma of the pancreasafter chemotherapy. World J Surg Oncol 2009; 7: 22.
39. Mitry E, Fields AL, Bleiberg H, et al. Adjuvant chemotherapyafter potentially curative resection of metastases fromcolorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol 2008; 26 (30): 4906-11.
40. Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by humanpapillomavirus types 16 and 18 promotes the degradation ofp53. Cell 1990; 63 (6): 1129-36.
41. Durst M, Croce CM, Gissmann L, Schwarz E, Huebner K. Papillomavirus sequences integrate near cellular oncogenesin some cervical carcinomas. Proc Natl Acad Sci USA 1987; 84 (4): 1070-4.
42. Alnemri ES, Livingston DJ, Nicholson DW, et al. Human ICE/CED-3 protease nomenclature. Cell 1996; 87 (2): 171.
43. Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR. The C.elegans cell death gene ced-3 encodes a protein similar tomammalian interleukin-1 beta-converting enzyme. Cell 1993; 75 (4): 641-52.
44. Salvesen GS. Caspases: opening the boxes and interpretingthe arrows. Cell Death Differ 2002; 9 (1): 3-5.
45. Fuentes-Prior P, Salvesen GS. The protein structures thatshape caspase activity, specificity, activation and inhibition. Biochem J 2004; 384 (Pt 2): 201-32.
46. Fischer H, Koenig U, Eckhart L, Tschachler E. Humancaspase 12 has acquired deleterious mutations. Biochem Biophys Res Commun 2002; 293 (2): 722-6.
47. Kachapati K, O'Brien TR, Bergeron J, Zhang M, Dean M. Population distribution of the functional caspase-12 allele. Hum Mutat 2006; 27 (9): 975.
48. Wang S, Miura M, Jung YK, Zhu H, Li E, Yuan J. Murinecaspase-11, an ICE-interacting protease, is essential for theactivation of ICE. Cell 1998; 92 (4): 501-9.
49. Martinon F, Burns K, Tschopp J. The inflammasome: amolecular platform triggering activation of inflammatorycaspases and processing of proIL-beta. Mol Cell 2002; 10 (2): 417-26.
50. Kalai M, Lamkanfi M, Denecker G, Boogmans M, Lippens S, Meeus A, et al. Regulation of the expression and processingof caspase-12. J Cell Biol 2003; 162 (3): 457-67.
51. Kuida K, Lippke JA, Ku G, et al. Altered cytokine export andapoptosis in mice deficient in interleukin-1 beta convertingenzyme. Science 1995; 267 (5206): 2000-3.
52. Lippens S, Kockx M, Knaapen M, et al. Epidermaldifferentiation does not involve the pro-apoptotic executionercaspases, but is associated with caspase-14 induction andprocessing. Cell Death Differ 2000; 7 (12): 1218-24.
53. Lippens S, Denecker G, Ovaere P, Vandenabeele P, Declercq W. Death penalty for keratinocytes: apoptosisversus cornification. Cell Death Differ 2005; 12 Suppl 2: 1497-508.
54. Liu H, Chang DW, Yang X. Interdimer processing andlinearity of procaspase-3 activation. A unifying mechanismfor the activation of initiator and effector caspases. J Biol Chem 2005; 280 (12): 11578-82.
55. Hughes MA, Harper N, Butterworth M, Cain K, Cohen GM, MacFarlane M. Reconstitution of the death-inducing signalingcomplex reveals a substrate switch that determines CD95-mediated death or survival. Mol Cell 2009; 35 (3): 265-79.
56. Zou H, Li Y, Liu X, Wang X. An APAF-1.cytochrome cmultimeric complex is a functional apoptosome that activatesprocaspase-9. J Biol Chem 1999; 274 (17): 11549-56.
57. Medema JP, Scaffidi C, Kischkel FC, et al. FLICE isactivated by association with the CD95 death-inducingsignaling complex (DISC). EMBO J 1997; 16 (10): 2794-804.
58. Bao Q, Shi Y. Apoptosome: a platform for the activation ofinitiator caspases. Cell Death Differ 2006; 14 (1): 56-65.
59. Tinel A, Tschopp J. The PIDDosome, a protein compleximplicated in activation of caspase-2 in response togenotoxic stress. Science 2004; 304 (5672): 843-6.
60. Pennarun B, Meijer A, de Vries EG, Kleibeuker JH, Kruyt F, de Jong S. Playing the DISC: turning on TRAIL deathreceptor-mediated apoptosis in cancer. Biochim Biophys Acta 2010; 1805 (2): 123-40.
61. Lovell JF, Billen LP, Bindner S, et al. Membrane binding bytBid initiates an ordered series of events culminating inmembrane permeabilization by Bax. Cell 2008; 135 (6): 1074-84.
62. Stennicke HR, Renatus M, Meldal M, Salvesen GS. Internallyquenched fluorescent peptide substrates disclose the subsitepreferences of human caspases 1, 3, 6, 7 and 8. Biochem J 2000; 350 Pt 2: 563-8.
63. Scaffidi C, Medema JP, Krammer PH, Peter ME. FLICE ispredominantly expressed as two functionally active isoforms, caspase-8/a and caspase-8/b. J Biol Chem 1997; 272 (43): 26953-8.
64. Ng PW, Porter AG, Janicke RU. Molecular cloning andcharacterization of two novel pro-apoptotic isoforms ofcaspase-10. J Biol Chem 1999; 274 (15): 10301-8.
65. Stennicke HR, Jurgensmeier JM, Shin H, et al. Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem 1998; 273 (42): 27084-90.
66. Sprick MR, Rieser E, Stahl H, Grosse-Wilde A, Weigand MA, Walczak H. Caspase-10 is recruited to and activated at thenative TRAIL and CD95 death-inducing signalling complexesin a FADD-dependent manner but can not functionallysubstitute caspase-8. EMBO J 2002; 21 (17): 4520-30.
67. Engels IH, Totzke G, Fischer U, Schulze-Osthoff K, Janicke RU. Caspase-10 sensitizes breast carcinoma cells to TRAILinducedbut not tumor necrosis factor-induced apoptosis in acaspase-3-dependent manner. Mol Cell Biol 2005; 25 (7): 2808-18.
68. Fischer U, Stroh C, Schulze-Osthoff K. Unique andoverlapping substrate specificities of caspase-8 andcaspase-10. Oncogene 2006; 25 (1): 152-9.
69. Lemmers B, Salmena L, Bidere N, et al. Essential role forcaspase-8 in Toll-like receptors and NFkappa B signaling. JBiol Chem 2007; 282 (10): 7416-23.
70. Chun HJ, Zheng L, Ahmad M, et al. Pleiotropic defects inlymphocyte activation caused by caspase-8 mutations leadto human immunodeficiency. Nature 2002; 419 (6905): 395-9.
71. Wang J, Zheng L, Lobito A, et al. Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cellapoptosis in autoimmune lymphoproliferative syndrome typeII. Cell 1999; 98 (1): 47-58.
72. Gronbaek K, Dalby T, Zeuthen J, Ralfkiaer E, Guidberg P. The V410I (G 1228A) variant of the caspase-10 gene is acommon polymorphism of the Danish population. Blood 2000; 95 (6): 2184-5.
73. Cerutti E, Campagnoli MF, Ferretti M, et al. Co-inheritedmutations of Fas and caspase-10 in development of theautoimmune lymphoproliferative syndrome. BMC Immunol 2007; 8: 28.
74. Varfolomeev EE, Schuchmann M, Luria V, et al. Targeteddisruption of the mouse Caspase 8 gene ablates cell deathinduction by the TNF receptors, Fas/Apo1, and DR3 and islethal prenatally. Immunity 1998; 9 (2): 267-76.
75. Reed JC, Doctor K, Rojas A, et al. Comparative analysis ofapoptosis and inflammation genes of mice and humans. Genome Res 2003; 13 (6B): 1376-88.
76. Kischkel FC, Lawrence DA, Tinel A, et al. Death receptorrecruitment of endogenous caspase-10 and apoptosisinitiation in the absence of caspase-8. J Biol Chem 2001; 276 (49): 46639-46.
77. Park WS, Lee JH, Shin MS, et al. Inactivating mutations ofthe caspase-10 gene in gastric cancer. Oncogene 2002; 21 (18): 2919-25.
78. Maelfait J, Beyaert R. Non-apoptotic functions of caspase-8. Biochem Pharmacol 2008; 76 (11): 1365-73.
79. Bodmer JL, Schneider P, Tschopp J. The moleculararchitecture of the TNF superfamily. Trends Biochem Sci 2002; 27 (1): 19-26.
80. Tartaglia LA, Weber RF, Figari IS, Reynolds C, Palladino MA, Jr., Goeddel DV. The two different receptors for tumornecrosis factor mediate distinct cellular responses. Proc Natl Acad Sci USA 1991; 88 (20): 9292-6.
81. Itoh N, Yonehara S, Ishii A, et al. The polypeptide encodedby the cDNA for human cell surface antigen Fas can mediateapoptosis. Cell 1991; 66 (2): 233-43.
82. Pan G, O'Rourke K, Chinnaiyan AM, et al. The receptor forthe cytotoxic ligand TRAIL. Science 1997; 276 (5309): 111-3.
83. Walczak H, Degli-Esposti MA, Johnson RS, et al. TRAIL-R2:a novel apoptosis-mediating receptor for TRAIL. EMBO J 1997; 16 (17): 5386-97.
84. MacFarlane M, Ahmad M, Srinivasula SM, Fernandes-Alnemri T, Cohen GM, Alnemri ES. Identification andmolecular cloning of two novel receptors for the cytotoxicligand TRAIL. J Biol Chem 1997; 272 (41): 25417-20.
85. Neumann L, Pforr C, Beaudouin J, et al. Dynamics within the CD95 death-inducing signaling complex decide life and deathof cells. Mol Syst Biol 2010; 6: 352.
86. Fricker N, Beaudouin J, Richter P, Eils R, Krammer PH, Lavrik IN. Model-based dissection of CD95 signalingdynamics reveals both a pro- and antiapoptotic role of c-FLIPL. J Cell Biol 2010; 190 (3): 377-89.
87. Walczak H, Miller RE, Ariail K, et al. Tumoricidal activity oftumor necrosis factor-related apoptosis-inducing ligand invivo. Nat Med 1999; 5 (2): 157-63.
88. Ashkenazi A, Pai RC, Fong S, et al. Safety and antitumoractivity of recombinant soluble Apo2 ligand. J Clin Invest 1999; 104 (2): 155-62.
89. Newsom-Davis T, Prieske S, Walczak H. Is TRAIL the holygrail of cancer therapy? Apoptosis 2009; 14 (4): 607-23.
90. Wiley SR, Schooley K, Smolak PJ, et al. Identification andcharacterization of a new member of the TNF family thatinduces apoptosis. Immunity 1995; 3 (6): 673-82.
91. Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A. Induction of apoptosis by Apo-2 ligand, a newmember of the tumor necrosis factor cytokine family. J Biol Chem 1996; 271 (22): 12687-90.
92. Smyth MJ, Cretney E, Takeda K, et al. Tumor necrosisfactor-related apoptosis-inducing ligand (TRAIL) contributesto interferon gamma-dependent natural killer cell protectionfrom tumor metastasis. J Exp Med 2001; 193 (6): 661-70.
93. Bodmer JL, Meier P, Tschopp J, Schneider P. Cysteine 230is essential for the structure and activity of the cytotoxicligand TRAIL. J Biol Chem 2000; 275 (27): 20632-7.
94. Hymowitz SG, O'Connell MP, Ultsch MH, et al. A uniquezinc-binding site revealed by a high-resolution X-ray structureof homotrimeric Apo2L/TRAIL. Biochemistry 2000; 39 (4): 633-40.
95. Mongkolsapaya J, Grimes JM, Chen N, et al. Structure of the TRAIL-DR5 complex reveals mechanisms conferringspecificity in apoptotic initiation. Nat Struct Biol 1999; 6 (11): 1048-53.
96. Scott FL, Stec B, Pop C, et al. The Fas-FADD death domaincomplex structure unravels signalling by receptor clustering. Nature 2009; 457 (7232): 1019-22.
97. Falschlehner C, Emmerich CH, Gerlach B, Walczak H. TRAIL signalling: Decisions between life and death. Int J Biochem Cell Biol 2007.
98. Bin L, Thorburn J, Thomas LR, Clark PE, Humphreys R, Thorburn A. Tumor-derived mutations in the TRAIL receptorDR5 inhibit TRAIL signaling through the DR4 receptor bycompeting for ligand binding. J Biol Chem 2007; 282 (38): 28189-94.
99. Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A. Apo2L/TRAIL-dependent recruitment ofendogenous FADD and caspase-8 to death receptors 4 and5. Immunity 2000; 12 (6): 611-20.
100. Tur V, van der Sloot AM, Reis CR, et al. DR4-selective tumornecrosis factor-related apoptosis-inducing ligand (TRAIL)variants obtained by structure-based design. J Biol Chem 2008; 283 (29): 20560-8.
101. van der Sloot AM, Tur V, Szegezdi E, et al. Designed tumornecrosis factor-related apoptosis-inducing ligand variantsinitiating apoptosis exclusively va the DR5 receptor. Proc Natl Acad Sci USA 2006; 103 (23): 8634-9.
102. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM. An antagonistdecoy receptor and a death domain-containing receptor for TRAIL. Science 1997; 277 (5327): 815-8.
103. Degli-Esposti MA, Smolak PJ, Walczak H, et al. Cloning andcharacterization of TRAIL-R3, a novel member of theemerging TRAIL receptor family. J Exp Med 1997; 186 (7): 1165-70.
104. Sheridan JP, Marsters SA, Pitti RM, et al. Control of TRAILinducedapoptosis by a family of signaling and decoyreceptors. Science 1997; 277 (5327): 818-21.
105. Schneider P, Bodmer JL, Thome M, Hofmann K, Holler N, Tschopp J. Characterization of two receptors for TRAIL. FEBS Lett 1997; 416 (3): 329-34.
106. Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG. The novel receptor TRAIL-R4induces NF-kappaB and protects against TRAIL-mediatedapoptosis, yet retains an incomplete death domain. Immunity 1997; 7 (6): 813-20.
107. Marsters SA, Sheridan JP, Pitti RM, et al. A novel receptorfor Apo2L/TRAIL contains a truncated death domain. Curr Biol 1997; 7 (12): 1003-6.
108. Emery JG, McDonnell P, Burke MB, et al. Osteoprotegerin isa receptor for the cytotoxic ligand TRAIL. J Biol Chem 1998; 273 (23): 14363-7.
109. Merino D, Lalaoui N, Morizot A, Schneider P, Solary E, Micheau O. Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2. Mol Cell Biol 2006; 26 (19): 7046-55.
110. Mirandola P, Ponti C, Gobbi G, et al. Activated human NKand CD8+ T cells express both TNF-related apoptosisinducingligand (TRAIL) and TRAIL receptors but areresistant to TRAIL-mediated cytotoxicity. Blood 2004; 104 (8): 2418-24.
111. Schultz DR, Harrington WJ, Jr. Apoptosis: programmed celldeath at a molecular level. Semin Arthritis Rheum 2003; 32 (6): 345-69.
112. Wang L, Yang JK, Kabaleeswaran V, et al. The Fas-FADDdeath domain complex structure reveals the basis of DISCassembly and disease mutations. Nat Struct Mol Biol 2010.
113. Carrington PE, Sandu C, Wei Y, et al. The structure of FADDand its mode of interaction with procaspase-8. Mol Cell 2006; 22 (5): 599-610.
114. Schutze S, Tchikov V, Schneider-Brachert W. Regulation of TNFR1 and CD95 signalling by receptorcompartmentalization. Nat Rev Mol Cell Biol 2008; 9 (8): 655-62.
115. Salvesen GS, Dixit VM. Caspase activation: the inducedproximitymodel. Proc Natl Acad Sci USA 1999; 96 (20): 10964-7.
116. Chang DW, Xing Z, Capacio VL, Peter ME, Yang X. Interdimer processing mechanism of procaspase-8activation. EMBO J 2003; 22 (16): 4132-42.
117. Boatright KM, Renatus M, Scott FL, et al. A unified model forapical caspase activation. Mol Cell 2003; 11 (2): 529-41.
118. Pop C, Fitzgerald P, Green DR, Salvesen GS. Role ofproteolysis in caspase-8 activation and stabilization. Biochemistry 2007; 46 (14): 4398-407.
119. Lavrik IN, Golks A, Riess D, Bentele M, Eils R, Krammer PH. Analysis of CD95 threshold signaling: triggering of CD95 (FAS/APO-1) at low concentrations primarily results insurvival signaling. J Biol Chem 2007; 282 (18): 13664-71.
120. Chang DW, Xing Z, Pan Y, et al. c-FLIP(L) is a dual functionregulator for caspase-8 activation and CD95-mediatedapoptosis. EMBO J 2002; 21 (14): 3704-14.
121. Golks A, Brenner D, Fritsch C, Krammer PH, Lavrik IN. c-FLIPR, a new regulator of death receptor-induced apoptosis. J Biol Chem 2005; 280 (15): 14507-13.
122. Yu JW, Shi Y. FLIP and the death effector domain family. Oncogene 2008; 27 (48): 6216-27.
123. Neumann L, Pforr C, Beaudouin J, et al. Dynamics within the CD95 death-inducing signaling complex decide life and deathof cells. Mol Syst Biol 2010; 6: 352.
124. Boatright KM, Deis C, Denault JB, Sutherlin DP, Salvesen GS. Activation of caspases-8 and -10 by FLIP(L). Biochem J 2004; 382 (Pt 2): 651-7.
125. Peter ME. The flip side of FLIP. Biochem J 2004; 382 (Pt 2):e1-3.
126. Yu JW, Jeffrey PD, Shi Y. Mechanism of procaspase-8activation by c-FLIPL. Proc Natl Acad Sci USA 2009; 106 (20): 8169-74.
127. Micheau O, Thome M, Schneider P, et al. The long form of FLIP is an activator of caspase-8 at the Fas death-inducingsignaling complex. J Biol Chem 2002; 277 (47): 45162-71.
128. Harper N, Farrow SN, Kaptein A, Cohen GM, MacFarlane M. Modulation of tumor necrosis factor apoptosis-inducingligand- induced NF-kappa B activation by inhibition of apicalcaspases. J Biol Chem 2001; 276 (37): 34743-52.
129. Kataoka T, Tschopp J. N-terminal fragment of c-FLIP(L)processed by caspase 8 specifically interacts with TRAF2and induces activation of the NF-kappaB signaling pathway. Mol Cell Biol 2004; 24 (7): 2627-36.
130. Wong WW, Gentle IE, Nachbur U, Anderton H, Vaux DL, Silke J. RIPK1 is not essential for TNFR1-induced activationof NF-kappaB. Cell Death Differ 2010; 17 (3): 482-7.
131. Golks A, Brenner D, Krammer PH, Lavrik IN. The c-FLIPNH2terminus (p 22-FLIP) induces NF-kappaB activation. JExp Med 2006; 203 (5): 1295-305.
132. Ashkenazi A, Pai RC, Fong S, et al. Safety and antitumoractivity of recombinant soluble Apo2 ligand. J Clin Invest 1999; 104 (2): 155-62.
133. Newsom-Davis T, Prieske S, Walczak H. Is TRAIL the holygrail of cancer therapy? Apoptosis 2009; 14 (4): 607-23.
134. Wiley SR, Schooley K, Smolak PJ, et al. Identification andcharacterization of a new member of the TNF family thatinduces apoptosis. Immunity 1995; 3 (6): 673-82.
135. Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A. Induction of apoptosis by Apo-2 ligand, a newmember of the tumor necrosis factor cytokine family. J Biol Chem 1996; 271 (22): 12687-90.
136. Smyth MJ, Cretney E, Takeda K, et al. Tumor necrosisfactor-related apoptosis-inducing ligand (TRAIL) contributesto interferon gamma-dependent natural killer cell protectionfrom tumor metastasis. J Exp Med 2001; 193 (6): 661-70.
137. Bodmer JL, Meier P, Tschopp J, Schneider P. Cysteine 230is essential for the structure and activity of the cytotoxicligand TRAIL. J Biol Chem 2000; 275 (27): 20632-7.
138. Hymowitz SG, O'Connell MP, Ultsch MH, et al. A uniquezinc-binding site revealed by a high-resolution X-ray structureof homotrimeric Apo2L/TRAIL. Biochemistry 2000; 39 (4): 633-40.
139. Mongkolsapaya J, Grimes JM, Chen N, et al. Structure of the TRAIL-DR5 complex reveals mechanisms conferringspecificity in apoptotic initiation. Nat Struct Biol 1999; 6 (11): 1048-53.
140. Scott FL, Stec B, Pop C, et al. The Fas-FADD death domaincomplex structure unravels signalling by receptor clustering. Nature 2009; 457 (7232): 1019-22.
141. Falschlehner C, Emmerich CH, Gerlach B, Walczak H. TRAIL signalling: Decisions between life and death. Int J Biochem Cell Biol 2007.
142. Bin L, Thorburn J, Thomas LR, Clark PE, Humphreys R, Thorburn A. Tumor-derived mutations in the TRAIL receptorDR5 inhibit TRAIL signaling through the DR4 receptor bycompeting for ligand binding. J Biol Chem 2007; 282 (38): 28189-94.
143. Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A. Apo2L/TRAIL-dependent recruitment ofendogenous FADD and caspase-8 to death receptors 4 and5. Immunity 2000; 12 (6): 611-20.
144. Tur V, van der Sloot AM, Reis CR, et al. DR4-selective tumornecrosis factor-related apoptosis-inducing ligand (TRAIL)variants obtained by structure-based design. J Biol Chem 2008; 283 (29): 20560-8.
145. van der Sloot AM, Tur V, Szegezdi E, et al. Designed tumornecrosis factor-related apoptosis-inducing ligand variantsinitiating apoptosis exclusively va the DR5 receptor. Proc Natl Acad Sci USA 2006; 103 (23): 8634-9.
146. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM. An antagonistdecoy receptor and a death domain-containing receptor for TRAIL. Science 1997; 277 (5327): 815-8.
147. Degli-Esposti MA, Smolak PJ, Walczak H, et al. Cloning andcharacterization of TRAIL-R3, a novel member of theemerging TRAIL receptor family. J Exp Med 1997; 186 (7): 1165-70.
148. Sheridan JP, Marsters SA, Pitti RM, et al. Control of TRAILinducedapoptosis by a family of signaling and decoyreceptors. Science 1997; 277 (5327): 818-21.
149. Schneider P, Bodmer JL, Thome M, Hofmann K, Holler N, Tschopp J. Characterization of two receptors for TRAIL. FEBS Lett 1997; 416 (3): 329-34.
150. Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG. The novel receptor TRAIL-R4induces NF-kappaB and protects against TRAIL-mediatedapoptosis, yet retains an incomplete death domain. Immunity 1997; 7 (6): 813-20.
151. Marsters SA, Sheridan JP, Pitti RM, et al. A novel receptorfor Apo2L/TRAIL contains a truncated death domain. Curr Biol 1997; 7 (12): 1003-6.
152. Emery JG, McDonnell P, Burke MB, et al. Osteoprotegerin isa receptor for the cytotoxic ligand TRAIL. J Biol Chem 1998; 273 (23): 14363-7.
153. Merino D, Lalaoui N, Morizot A, Schneider P, Solary E, Micheau O. Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2. Mol Cell Biol 2006; 26 (19): 7046-55.
154. Mirandola P, Ponti C, Gobbi G, et al. Activated human NKand CD8+ T cells express both TNF-related apoptosisinducingligand (TRAIL) and TRAIL receptors but areresistant to TRAIL-mediated cytotoxicity. Blood 2004; 104 (8): 2418-24.
155. Schultz DR, Harrington WJ, Jr. Apoptosis: programmed celldeath at a molecular level. Semin Arthritis Rheum 2003; 32 (6): 345-69.
156. Wang L, Yang JK, Kabaleeswaran V, et al. The Fas-FADDdeath domain complex structure reveals the basis of DISCassembly and disease mutations. Nat Struct Mol Biol 2010.
157. Carrington PE, Sandu C, Wei Y, et al. The structure of FADDand its mode of interaction with procaspase-8. Mol Cell 2006; 22 (5): 599-610.
158. Schutze S, Tchikov V, Schneider-Brachert W. Regulation of TNFR1 and CD95 signalling by receptorcompartmentalization. Nat Rev Mol Cell Biol 2008; 9 (8): 655-62.
159. Salvesen GS, Dixit VM. Caspase activation: the inducedproximitymodel. Proc Natl Acad Sci USA 1999; 96 (20): 10964-7.
160. Chang DW, Xing Z, Capacio VL, Peter ME, Yang X. Interdimer processing mechanism of procaspase-8activation. EMBO J 2003; 22 (16): 4132-42.
161. Boatright KM, Renatus M, Scott FL, et al. A unified model forapical caspase activation. Mol Cell 2003; 11 (2): 529-41.
162. Pop C, Fitzgerald P, Green DR, Salvesen GS. Role ofproteolysis in caspase-8 activation and stabilization. Biochemistry 2007; 46 (14): 4398-407.
163. Lavrik IN, Golks A, Riess D, Bentele M, Eils R, Krammer PH. Analysis of CD95 threshold signaling: triggering of CD95 (FAS/APO-1) at low concentrations primarily results insurvival signaling. J Biol Chem 2007; 282 (18): 13664-71.
164. Chang DW, Xing Z, Pan Y, et al. c-FLIP(L) is a dual functionregulator for caspase-8 activation and CD95-mediatedapoptosis. EMBO J 2002; 21 (14): 3704-14.
165. Golks A, Brenner D, Fritsch C, Krammer PH, Lavrik IN. c-FLIPR, a new regulator of death receptor-induced apoptosis. J Biol Chem 2005; 280 (15): 14507-13.
166. Yu JW, Shi Y. FLIP and the death effector domain family. Oncogene 2008; 27 (48): 6216-27.
167. Neumann L, Pforr C, Beaudouin J, et al. Dynamics within the CD95 death-inducing signaling complex decide life and deathof cells. Mol Syst Biol 2010; 6: 352.
168. Boatright KM, Deis C, Denault JB, Sutherlin DP, Salvesen GS. Activation of caspases-8 and -10 by FLIP(L). Biochem J 2004; 382 (Pt 2): 651-7.
169. Peter ME. The flip side of FLIP. Biochem J 2004; 382 (Pt 2):e1-3.
170. Yu JW, Jeffrey PD, Shi Y. Mechanism of procaspase-8activation by c-FLIPL. Proc Natl Acad Sci USA 2009; 106 (20): 8169-74.
171. Micheau O, Thome M, Schneider P, et al. The long form of FLIP is an activator of caspase-8 at the Fas death-inducingsignaling complex. J Biol Chem 2002; 277 (47): 45162-71.
172. Harper N, Farrow SN, Kaptein A, Cohen GM, MacFarlane M. Modulation of tumor necrosis factor apoptosis-inducingligand- induced NF-kappa B activation by inhibition of apicalcaspases. J Biol Chem 2001; 276 (37): 34743-52.
173. Kataoka T, Tschopp J. N-terminal fragment of c-FLIP(L)processed by caspase 8 specifically interacts with TRAF2and induces activation of the NF-kappaB signaling pathway. Mol Cell Biol 2004; 24 (7): 2627-36.
174. Wong WW, Gentle IE, Nachbur U, Anderton H, Vaux DL, Silke J. RIPK1 is not essential for TNFR1-induced activationof NF-kappaB. Cell Death Differ 2010; 17 (3): 482-7.
175. Golks A, Brenner D, Krammer PH, Lavrik IN. The c-FLIPNH2terminus (p 22-FLIP) induces NF-kappaB activation. JExp Med 2006; 203 (5): 1295-305.
176. Antonsson B, Montessuit S, Lauper S, Eskes R, Martinou JC. Bax oligomerization is required for channel-forming activity inliposomes and to trigger cytochrome c release frommitochondria. Biochem J 2000; 345 Pt 2: 271-8.
177. Dussmann H, Rehm M, Concannon CG, et al. Single-cellquantification of Bax activation and mathematical modellingsuggest pore formation on minimal mitochondrial Baxaccumulation. Cell Death Differ 2010; 17 (2): 278-90.
178. Eskes R, Antonsson B, Osen-Sand A, et al. Bax-inducedcytochrome C release from mitochondria is independent ofthe permeability transition pore but highly dependent on Mg2+ ions. J Cell Biol 1998; 143 (1): 217-24.
179. Chipuk JE, Bouchier-Hayes L, Green DR. Mitochondrialouter membrane permeabilization during apoptosis: theinnocent bystander scenario. Cell Death Differ 2006; 13 (8): 1396-402.
180. Kuwana T, Mackey MR, Perkins G, et al. Bid, Bax, and lipidscooperate to form supramolecular openings in the outermitochondrial membrane. Cell 2002; 111 (3): 331-42.
181. Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. Therelease of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 1997; 275 (5303): 1132-6.
182. Dussmann H, Rehm M, Kogel D, Prehn JH. Outermitochondrial membrane permeabilization during apoptosistriggers caspase-independent mitochondrial and caspasedependentplasma membrane potential depolarization: asingle-cell analysis. J Cell Sci 2003; 116 (Pt 3): 525-36.
183. Varnes ME, Chiu SM, Xue LY, Oleinick NL. Photodynamictherapy-induced apoptosis in lymphoma cells: translocationof cytochrome c causes inhibition of respiration as well ascaspase activation. Biochem Biophys Res Commun 1999; 255 (3): 673-9.
184. Faccio L, Fusco C, Chen A, Martinotti S, Bonventre JV, Zervos AS. Characterization of a novel human serineprotease that has extensive homology to bacterial heat shockendoprotease HtrA and is regulated by kidney ischemia. JBiol Chem 2000; 275 (4): 2581-8.
185. Rehm M, Huber HJ, Hellwig CT, Anguissola S, Dussmann H, Prehn JH. Dynamics of outer mitochondrial membranepermeabilization during apoptosis. Cell Death Differ 2009; 16 (4): 613-23.
186. Munoz-Pinedo C, Guio-Carrion A, Goldstein JC, Fitzgerald P, Newmeyer DD, Green DR. Different mitochondrialintermembrane space proteins are released during apoptosisin a manner that is coordinately initiated but can vary induration. Proc Natl Acad Sci USA 2006; 103 (31): 11573-8.
187. Arnoult D, Gaume B, Karbowski M, Sharpe JC, Cecconi F, Youle RJ. Mitochondrial release of AIF and EndoG requirescaspase activation downstream of Bax/Bak-mediatedpermeabilization. EMBO J 2003; 22 (17): 4385-99.
188. Flanagan L, Sebastia J, Tuffy LP, et al. XIAP impairs Smacrelease from the mitochondria during apoptosis. Cell Deathand Dis 2010; 1: e49.
189. Zhou P, Chou J, Olea RS, Yuan J, Wagner G. Solutionstructure of Apaf-1 CARD and its interaction with caspase-9CARD: a structural basis for specific adaptor/caspaseinteraction. Proc Natl Acad Sci USA 1999; 96 (20): 11265-70.
190. Adrain C, Slee EA, Harte MT, Martin SJ. Regulation ofapoptotic protease activating factor-1 oligomerization andapoptosis by the WD-40 repeat region. J Biol Chem 1999; 274 (30): 20855-60.
191. Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X, Akey CW. Three-dimensional structure of the apoptosome:implications for assembly, procaspase-9 binding, andactivation. Mol Cell 2002; 9 (2): 423-32.
192. Cain K, Bratton SB, Langlais C, et al. Apaf-1 oligomerizesinto biologically active approximately 700-kDa and inactiveapproximately 1.4-MDa apoptosome complexes. J Biol Chem 2000; 275 (9): 6067-70.
193. Twiddy D, Brown DG, Adrain C, et al. Pro-apoptotic proteinsreleased from the mitochondria regulate the proteincomposition and caspase-processing activity of the nativeApaf-1/caspase-9 apoptosome complex. J Biol Chem 2004; 279 (19): 19665-82.
194. Renatus M, Stennicke HR, Scott FL, Liddington RC, Salvesen GS. Dimer formation drives the activation of thecell death protease caspase 9. Proc Natl Acad Sci USA 2001; 98 (25): 14250-5.
195. Stennicke HR, Deveraux QL, Humke EW, Reed JC, Dixit VM, Salvesen GS. Caspase-9 can be activated withoutproteolytic processing. J Biol Chem 1999; 274 (13): 8359-62.
196. Shi Y. Caspase activation: revisiting the induced proximitymodel. Cell 2004; 117 (7): 855-8.
197. Li P, Nijhawan D, Budihardjo I, et al. Cytochrome c anddATP-dependent formation of Apaf-1/caspase-9 complexinitiates an apoptotic protease cascade. Cell 1997; 91 (4): 479-89.
198. Twiddy D, Cohen GM, Macfarlane M, Cain K. Caspase-7 isdirectly activated by the approximately 700-kDa apoptosomecomplex and is released as a stable XIAP-caspase-7approximately 200-kDa complex. J Biol Chem 2006; 281 (7): 3876-88.
199. Denault JB, Eckelman BP, Shin H, Pop C, Salvesen GS. Caspase 3 attenuates XIAP (X-linked inhibitor of apoptosisprotein)-mediated inhibition of caspase 9. Biochem J 2007; 405 (1): 11-9.
200. Malladi S, Challa-Malladi M, Fearnhead HO, Bratton SB. The Apaf-1[bull]procaspase-9 apoptosome complex functions asa proteolytic-based molecular timer. EMBO J 2009; 28 (13): 1916-25.
201. Eckelman BP, Salvesen GS, Scott FL. Human inhibitor ofapoptosis proteins: why XIAP is the black sheep of thefamily. EMBO Rep 2006; 7 (10): 988-94.
202. Schimmer AD, Dalili S, Batey RA, Riedl SJ. Targeting XIAPfor the treatment of malignancy. Cell Death Differ 2006; 13 (2): 179-88.
203. Shiozaki EN, Chai J, Rigotti DJ, et al. Mechanism of XIAPmediatedinhibition of caspase-9. Mol Cell 2003; 11 (2): 519-27.
204. Suzuki Y, Nakabayashi Y, Nakata K, Reed JC, Takahashi R. X-linked inhibitor of apoptosis protein (XIAP) inhibitscaspase-3 and -7 in distinct modes. J Biol Chem 2001; 276 (29): 27058-63.
205. Scott FL, Denault JB, Riedl SJ, Shin H, Renatus M, Salvesen GS. XIAP inhibits caspase-3 and -7 using two binding sites:evolutionarily conserved mechanism of IAPs. EMBO J 2005; 24 (3): 645-55.
206. Duckett CS, Nava VE, Gedrich RW, et al. A conserved familyof cellular genes related to the baculovirus iap gene andencoding apoptosis inhibitors. EMBO J 1996; 15 (11): 2685-94.
207. Riedl SJ, Renatus M, Schwarzenbacher R, et al. Structuralbasis for the inhibition of caspase-3 by XIAP. Cell 2001; 104 (5): 791-800.
208. O'Connor CL, Anguissola S, Huber HJ, Dussmann H, Prehn JH, Rehm M. Intracellular signaling dynamics duringapoptosis execution in the presence or absence of X-linkedinhibitor-of-apoptosis-protein. Biochim Biophys Acta 2008; 1783 (10): 1903-13.
209. Rehm M, Huber HJ, Dussmann H, Prehn JH. Systemsanalysis of effector caspase activation and its control by Xlinkedinhibitor of apoptosis protein. EMBO J 2006; 25 (18): 4338-49.
210. Eckelman BP, Salvesen GS. The human anti-apoptoticproteins cIAP1 and cIAP2 bind but do not inhibit caspases. JBiol Chem 2006; 281 (6): 3254-60.
211. Dubrez-Daloz L, Dupoux A, Cartier J. IAPs: more than justinhibitors of apoptosis proteins. Cell Cycle 2008; 7 (8): 1036-46.
212. Vaux DL, Silke J. IAPs, RINGs and ubiquitylation. Nat Rev Mol Cell Biol 2005; 6 (4): 287-97.
213. Choi YE, Butterworth M, Malladi S, Duckett CS, Cohen GM, Bratton SB. The E3 ubiquitin ligase cIAP1 binds andubiquitinates caspase-3 and -7 va unique mechanisms atdistinct steps in their processing. J Biol Chem 2009; 284 (19): 12772-82.
214. Srinivasula SM, Ashwell JD. IAPs: what's in a name? Mol Cell 2008; 30 (2): 123-35.
215. Chai J, Du C, Wu JW, Kyin S, Wang X, Shi Y. Structural andbiochemical basis of apoptotic activation by Smac/DIABLO. Nature 2000; 406 (6798): 855-62.
216. Liu Z, Sun C, Olejniczak ET, et al. Structural basis for bindingof Smac/DIABLO to the XIAP BIR3 domain. Nature 2000; 408 (6815): 1004-8.
217. Wu G, Chai J, Suber TL, et al. Structural basis of IAPrecognition by Smac/DIABLO. Nature 2000; 408 (6815): 1008-12.
218. Luthi AU, Martin SJ. The CASBAH: a searchable database ofcaspase substrates. Cell Death Differ 2007; 14 (4): 641-50.
219. Janicke RU, Sprengart ML, Wati MR, Porter AG. Caspase-3is required for DNA fragmentation and morphologicalchanges associated with apoptosis. J Biol Chem 1998; 273 (16): 9357-60.
220. Rehm M, Dussmann H, Janicke RU, Tavare JM, Kogel D, Prehn JH. Single-cell fluorescence resonance energytransfer analysis demonstrates that caspase activation duringapoptosis is a rapid process. Role of caspase-3. J Biol Chem 2002; 277 (27): 24506-14.
221. Huber HJ, Laussmann MA, Prehn JH, Rehm M. Diffusion iscapable of translating anisotropic apoptosis initiation into ahomogeneous execution of cell death. BMC Syst Biol 2010; 4 (1): 9.
222. Thornberry NA, Rano TA, Peterson EP, et al. A combinatorialapproach defines specificities of members of the caspasefamily and granzyme B. Functional relationships establishedfor key mediators of apoptosis. J Biol Chem 1997; 272 (29): 17907-11.
223. Harris JL, Backes BJ, Leonetti F, Mahrus S, Ellman JA, Craik CS. Rapid and general profiling of protease specificity byusing combinatorial fluorogenic substrate libraries. Proc Natl Acad Sci USA 2000; 97 (14): 7754-9.
224. Ju W, Valencia CA, Pang H, et al. Proteome-wideidentification of family member-specific natural substraterepertoire of caspases. Proc Natl Acad Sci USA 2007; 104 (36): 14294-9.
225. Garcia-Calvo M, Peterson EP, Leiting B, Ruel R, Nicholson DW, Thornberry NA. Inhibition of human caspases bypeptide-based and macromolecular inhibitors. J Biol Chem 1998; 273 (49): 32608-13.
226. Watt W, Koeplinger KA, Mildner AM, Heinrikson RL, Tomasselli AG, Watenpaugh KD. The atomic-resolutionstructure of human caspase-8, a key activator of apoptosis. Structure 1999; 7 (9): 1135-43.
227. Wei Y, Fox T, Chambers SP, et al. The structures ofcaspases-1, -3, -7 and -8 reveal the basis for substrate andinhibitor selectivity. Chem Biol 2000; 7 (6): 423-32.
228. Schweizer A, Briand C, Grutter MG. Crystal structure ofcaspase-2, apical initiator of the intrinsic apoptotic pathway. JBiol Chem 2003; 278 (43): 42441-7.
229. Rotonda J, Nicholson DW, Fazil KM, et al. The threedimensionalstructure of apopain/CPP32, a key mediator ofapoptosis. Nat Struct Biol 1996; 3 (7): 619-25.
230. Blanchard H, Donepudi M, Tschopp M, Kodandapani L, Wu JC, Grutter MG. Caspase-8 specificity probed at subsiteS(4): crystal structure of the caspase-8-Z-DEVD-chocomplex. J Mol Biol 2000; 302 (1): 9-16.
231. Mahrus S, Trinidad JC, Barkan DT, Sali A, Burlingame AL, Wells JA. Global sequencing of proteolytic cleavage sites inapoptosis by specific labeling of protein N termini. Cell 2008; 134 (5): 866-76.
232. Van Damme P, Martens L, Van Damme J, et al. Caspasespecificand nonspecific in vivo protein processing duringFas-induced apoptosis. Nat Methods 2005; 2 (10): 771-7.
233. Johnson CE, Kornbluth S. Caspase cleavage is not foreveryone. Cell 2008; 134 (5): 720-1.
234. Dix MM, Simon GM, Cravatt BF. Global mapping of thetopography and magnitude of proteolytic events in apoptosis. Cell 2008; 134 (4): 679-91.
235. Coleman ML, Sahai EA, Yeo M, Bosch M, Dewar A, Olson MF. Membrane blebbing during apoptosis results fromcaspase-mediated activation of ROCK I. Nat Cell Biol 2001; 3 (4): 339-45.
236. Woo EJ, Kim YG, Kim MS, et al. Structural mechanism forinactivation and activation of CAD/DFF40 in the apoptoticpathway. Mol Cell 2004; 14 (4): 531-9.
237. Nagata S. Apoptotic DNA fragmentation. Exp Cell Res 2000; 256 (1): 12-8.
238. Bader M, Steller H. Regulation of cell death by the ubiquitinproteasomesystem. Curr Opin Cell Biol 2009; 21 (6): 878-84.
239. Kurokawa M, Kornbluth S. Caspases and kinases in a deathgrip. Cell 2009; 138 (5): 838-54.
240. Moquin D, Chan FK. The molecular regulation ofprogrammed necrotic cell injury. Trends Biochem Sci 2010; 35 (8): 434-41.
241. Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G. Molecular mechanisms of necroptosis: an ordered cellularexplosion. Nat Rev Mol Cell Biol 2010; 11 (10): 700-14.
242. Albeck JG, Burke JM, Aldridge BB, Zhang M, Lauffenburger DA, Sorger PK. Quantitative analysis of pathways controllingextrinsic apoptosis in single cells. Mol Cell 2008; 30 (1): 11-25.
243. Lamkanfi M, Festjens N, Declercq W, Vanden Berghe T, Vandenabeele P. Caspases in cell survival, proliferation anddifferentiation. Cell Death Differ 2007; 14 (1): 44-55.
244. Levine B, Sinha S, Kroemer G. Bcl-2 family members: dualregulators of apoptosis and autophagy. Autophagy 2008; 4 (5): 600-6.
245. Rolland SG, Conradt B. New role of the BCL2 family ofproteins in the regulation of mitochondrial dynamics. Curr Opin Cell Biol 2010; 22 (6): 852-8.
246. Benard G, Bellance N, Jose C, Melser S, Nouette-Gaulain K, Rossignol R. Multi-site control and regulation ofmitochondrial energy production. Biochim Biophys Acta 2010; 1797 (6-7): 698-709.
247. Duncan JS, Turowec JP, Vilk G, Li SS, Gloor GB, Litchfield DW. Regulation of cell proliferation and survival:convergence of protein kinases and caspases. Biochim Biophys Acta 2010; 1804 (3): 505-10.