Mathematical modeling identifies inhibitors of apoptosis as mediators of positive feedback and bistability

PLoS Computational Biology

Volumn 2, Issue 9, 2006, Pages 1061-1073

  Legewie, Stefan ^a   Blüthgen, Nils ^a   Herzel, Hanspeter ^a  

^a HUMBOLDT UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CELL SIGNALING; CHEMICAL ACTIVATION; MITOCHONDRIA; PROTEINS;

APOPTOSIS INDUCTION; BI-STABILITY; CASPASE ACTIVATION; CASPASE-3; CELLULAR CONTEXTS; CYTOCHROME C; CYTOTOXIC; INHIBITOR OF APOPTOSIS; MITOCHONDRIAL PATHWAYS; MITOCHONDRIAS;

CELL DEATH;

CASPASE 3; CASPASE 9; INHIBITOR OF APOPTOSIS PROTEIN; X LINKED INHIBITOR OF APOPTOSIS; CASPASE; CASPASE INHIBITOR;

AMINO ACID SEQUENCE; ARTICLE; ENZYME ACTIVATION; ENZYME KINETICS; ENZYME STABILITY; FEEDBACK SYSTEM; MATHEMATICAL MODEL; MITOCHONDRION; POSITIVE FEEDBACK; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; APOPTOSIS; BIOLOGICAL MODEL; BIOLOGY; COMPUTER SIMULATION; KINETICS; METABOLISM; MOLECULAR GENETICS; TIME;

INTRACISTERNAL A-PARTICLES;

APOPTOSIS; CASPASE INHIBITORS; CASPASES; COMPUTATIONAL BIOLOGY; COMPUTER SIMULATION; ENZYME ACTIVATION; FEEDBACK, PHYSIOLOGICAL; INHIBITOR OF APOPTOSIS PROTEINS; KINETICS; MITOCHONDRIA; MODELS, BIOLOGICAL; MOLECULAR SEQUENCE DATA; SIGNAL TRANSDUCTION; TIME FACTORS;

EID: 33749370199     PISSN: 1553734X     EISSN: 15537358     Source Type: Journal    
DOI: 10.1371/journal.pcbi.0020120     Document Type: Article

References (109)

1. Chang HY, Yang X (2000) Proteases for cell suicide: Functions and regulation of caspases. Microbiol Mol Biol Rev 64: 821-846.
2. Salvesen GS, Duckett CS (2002) IAP proteins: Blocking the road to death's door. Nat Rev Mol Cell Biol 3: 401-410.
3. Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, et al. (1997) Prevention of apoptosis by Bcl-2: Release of cytochrome c from mitochondria blocked. Science 275: 1129-1132.
4. Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD (1997) The release of cytochrome c from mitochondria: A primary site for Bcl-2 regulation of apoptosis. Science 275: 1132-1136.
5. Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, et al. (1999) Ordering the cytochrome c-initiated caspase cascade: Hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol 144: 281-292.
6. Kluck RM, Ellerby LM, Ellerby HM, Naiem S, Yaffe MP, et al. (2000) Determinants of cytochrome c pro-apoptotic activity. The role of lysine 72 trimethylation. J Biol Chem 275: 16127-16133.
7. Murphy BM, O'Neill AJ, Adrain C, Watson RW, Martin SJ (2003) The apoptosome pathway to caspase activation in primary human neutrophils exhibits dramatically reduced requirements for cytochrome C. J Exp Med 197: 625-632.
8. Liu X, Kim CN, Yang J, Jemmerson R, Wang X (1996) Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c. Cell 86: 147-157.
9. Cain K, Langlais C, Sun XM, Brown DG, Cohen GM (2001) Physiological concentrations of K+ inhibit cytochrome c-dependent formation of the apoptosome. J Biol Chem 276: 41985-41990.
10. Nguyen JT, Wells JA (2003) Direct activation of the apoptosis machinery as a mechanism to target cancer cells. Proc Natl Acad Sci U S A 100: 7533-7538.
11. Martinou I, Desagher S, Eskes R, Antonsson B, Andre E, et al. (1999) The release of cytochrome c from mitochondria during apoptosis of NGF-deprived sympathetic neurons is a reversible event. J Cell Biol 144: 883-889.
12. Von Ahsen O, Waterhouse NJ, Kuwana T, Newmeyer DD, Green DR (2000) The "harmless" release of cytochrome c. Cell Death Differ 7: 1192-1199.
13. Oliver L, LeCabellec MT, Pradal G, Meflah K, Kroemer G, et al. (2005) Constitutive presence of cytochrome c in the cytosol of a chemoresistant leukemic cell line. Apoptosis 10: 277-287.
14. Waterhouse NJ, Goldstein JC, von Ahsen O, Schuler M, Newmeyer DD, et al. (2001) Cytochrome c maintains mitochondrial transmembrane potential and ATP generation after outer mitochondrial membrane permeabilization during the apoptotic process. J Cell Biol 153: 319-328.
15. Deshmukh M, Kuida K, Johnson EM Jr (2000) Caspase inhibition extends the commitment to neuronal death beyond cytochrome c release to the point of mitochondrial depolarization. J Cell Biol 150: 131-143.
16. Chang LK, Putcha GV, Deshmukh M, Johnson EM Jr (2002) Mitochondrial involvement in the point of no return in neuronal apoptosis. Biochimie 84: 223-231.
17. Chandra D, Liu JW, Tang DG (2002) Early mitochondrial activation and cytochrome c up-regulation during apoptosis. J Biol Chem 277: 50842-50854.
18. Martin AG, Fearnhead HO (2002) Apocytochrome c blocks caspase-9 activation and Bax-induced apoptosis. J Biol Chem 277: 50834-50841.
19. Perrelet D, Ferri A, Liston P, Muzzin P, Korneluk RG, et al. (2002) IAPs are essential for GDNF-mediated neuroprotective effects in injured motor neurons in vivo. Nat Cell Biol 4: 175-179.
20. Xu D, Bureau Y, McIntyre DC, Nicholson DW, Liston P, et al. (1999) Attenuation of ischemia-induced cellular and behavioral deficits by X chromosome-linked inhibitor of apoptosis protein overexpression in the rat hippocampus. J Neurosci 19: 5026-5033.
21. Kugler S, Straten G, Kreppel F, Isenmann S, Liston P, et al. (2000) The X-linked inhibitor of apoptosis (XIAP) prevents cell death in axotomized CNS neurons in vivo. Cell Death Differ 7: 815-824.
22. Eberhardt O, Coelln RV, Kugler S, Lindenau J, Rathke-Hartlieb S, et al. (2000) Protection by synergistic effects of adenovirus-mediated X-chromosome-linked inhibitor of apoptosis and glial cell line-derived neurotrophic factor gene transfer in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine model of Parkinson's disease. J Neurosci 20: 9126-9134.
23. Longthorne VL, Williams GT (1997) Caspase activity is required for commitment to Fas-mediated apoptosis. EMBO J 16: 3805-3812.
24. Wang K, Brems JJ, Gamelli RL, Ding J (2005) Reversibility of caspase activation and its role during glycochenodeoxycholate-induced hepatocyte apoptosis. J Biol Chem 280: 23490-23495.
25. Ferrell JE, Jr. (2002) Self-perpetuating states in signal transduction: Positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol 14: 140-148.
26. Cross FR, Archambault V, Miller M, Klovstad M (2002) Testing a mathematical model of the yeast cell cycle. Mol Biol Cell 13: 52-70.
27. Pomerening JR, Sontag ED, Ferrell JE, Jr. (2003) Building a cell cycle oscillator: Hysteresis and bistability in the activation of Cdc2. Nat Cell Biol 5: 346-351.
28. Sha W, Moore J, Chen K, Lassaletta AD, Yi CS, et al. (2003) Hysteresis drives cell-cycle transitions in Xenopus laevis egg extracts. Proc Natl Acad Sci U S A 100: 975-980.
29. Xiong W, Ferrell JE, Jr (2003) A positive-feedback-based bistable "memory module" that governs a cell fate decision. Nature 426: 460-465.
30. Markevich NI, Hoek JB, Kholodenko BN (2004) Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades. J Cell Biol 164: 353-359.
31. Hayer A, Bhalla US (2005) Molecular switches at the synapse emerge from receptor and kinase traffic. PLoS Comput Biol 1: 137-154.
32. Shiozaki EN, Chai J, Shi Y (2002) Oligomerization and activation of caspase-9, induced by Apaf-1 CARD. Proc Natl Acad Sci U S A 99: 4197-4202.
33. Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES (1998) Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization. Mol Cell 1: 949-957.
34. Zou H, Yang R, Hao J, Wang J, Sun C, et al. (2003) Regulation of the Apaf-1/caspase-9 apoptosome by caspase-3 and XIAP. J Biol Chem 278: 8091-8098.
35. Bratton SB, Walker G, Srinivasula SM, Sun XM, Butterworth M, et al. (2001) Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes. EMBO J 20: 998-1009.
36. Hill MM, Adrain C, Duriez PJ, Creagh EM, Martin SJ (2004) Analysis of the composition, assembly kinetics and activity of native Apaf-1 apoptosomes. EMBO J 23: 2134-2145.
37. Chao Y, Shiozaki EN, Srinivasula SM, Rigotti DJ, Fairman R, et al. (2005) Engineering a dimeric caspase-9: A re-evaluation of the induced proximity model for caspase activation. PLoS Biol 3: e183.
38. Rodriguez J, Lazebnik Y (1999) Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 13: 3179-3184.
39. Cain K, Bratton SB, Cohen GM (2002) The Apaf-1 apoptosome: A large caspase-activating complex. Biochimie 84: 203-214.
40. Han Z, Hendrickson EA, Bremner TA, Wyche JH (1997) A sequential two-step mechanism for the production of the mature p17:p12 form of caspase-3 in vitro. J Biol Chem 272: 13432-13436.
41. Stennicke HR, Jurgensmeier JM, Shin H, Deveraux Q, Wolf BB, et al. (1998) Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem 273: 27084-27090.
42. Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, Robertson N, Armstrong RC, et al. (1996) The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32. J Biol Chem 271: 27099-27106.
43. Fujita E, Egashira J, Urase K, Kuida K, Momoi T (2001) Caspase-9 processing by caspase-3 via a feedback amplification loop in vivo. Cell Death Differ 8: 335-344.
44. Blanc C, Deveraux QL, Krajewski S, Janicke RU, Porter AG, et al. (2000) Caspase-3 is essential for procaspase-9 processing and cisplatin-induced apoptosis of MCF-7 breast cancer cells. Cancer Res 60: 4386-4390.
45. Riedl SJ, Renatus M, Schwarzenbacher R, Zhou Q, Sun C, et al. (2001) Structural basis for the inhibition of caspase-3 by XIAP. Cell 104: 791-800.
46. Deveraux QL, Takahashi R, Salvesen GS, Reed JC (1997) X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388: 300-304.
47. Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, et al. (1998) IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J 17: 2215-2223.
48. Shiozaki EN, Chai J, Rigotti DJ, Riedl SJ, Li P, et al. (2003) Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell 11: 519-527.
49. Ekert PG, Silke J, Hawkins CJ, Verhagen AM, Vaux DL (2001) DIABLO promotes apoptosis by removing MIHA/XIAP from processed caspase 9. J Cell Biol 152: 483-490.
50. Eissing T, Conzelmann H, Gilles ED, Allgower F, Bullinger E, et al. (2004) Bistability analyses of a caspase activation model for receptor-induced apoptosis. J Biol Chem 279: 36892-36897.
51. Srinivasula SM, Hegde R, Saleh A, Datta P, Shiozaki E, et al. (2001) A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 410: 112-116.
52. Sun XM, Bratton SB, Butterworth M, MacFarlane M, Cohen GM (2002) Bcl-2 and Bcl-xL inhibit CD95-mediated apoptosis by preventing mitochondrial release of Smac/DIABLO and subsequent inactivation of X-linked inhibitor-of-apoptosis protein. J Biol Chem 277: 11345-11351.
53. Cosulich SC, Savory PJ, Clarke PR (1999) Bcl-2 regulates amplification of caspase activation by cytochrome c. Curr Biol 9: 147-150.
54. Bruey JM, Ducasse C, Bonniaud P, Ravagnan L, Susin SA, et al. (2000) Hsp27 negatively regulates cell death by interacting with cytochrome c. Nat Cell Biol 2: 645-652.
55. Chau BN, Cheng EH, Kerr DA, Hardwick JM (2000) Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1. Mol Cell 6: 31-40.
56. 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.
57. Rehm M, Dussmann H, Prehn JH (2003) Real-time single cell analysis of Smac/DIABLO release during apoptosis. J Cell Biol 162: 1031-1043.
58. Rehm M, Dussmann H, Janicke RU, Tavare JM, Kogel D, et al. (2002) Single-cell fluorescence resonance energy transfer analysis demonstrates that caspase activation during apoptosis is a rapid process. Role of caspase-3. J Biol Chem 277: 24506-24514.
59. Duckett CS, Li F, Wang Y, Tomaselli KJ, Thompson CB, et al. (1998) Human IAP-like protein regulates programmed cell death downstream of Bcl-xL and cytochrome c. Mol Cell Biol 18: 608-615.
60. Pollett JB, Zhu YX, Gandhi S, Bali M, Masih-Khan E, et al. (2003) RU486-inducible retrovirus-mediated caspase-3 overexpression is cytotoxic to bcl-xL-expressing myeloma cells in vitro and in vivo. Mol Ther 8: 230-237.
61. Yang X, Chang HY, Baltimore D (1998) Autoproteolytic activation of procaspases by oligomerization. Mol Cell 1: 319-325.
62. Boatright KM, Renatus M, Scott FL, Sperandio S, Shin H, et al. (2003) A unified model for apical caspase activation. Mol Cell 11: 529-541.
63. Cardone MH, Roy N, Stennicke HR, Salvesen GS, Franke TF, et al. (1998) Regulation of cell death protease caspase-9 by phosphorylation. Science 282: 1318-1321.
64. Tenev T, Marani M, McNeish I, Lemoine NR (2001) Pro-caspase-3 overexpression sensitises ovarian cancer cells to proteasome inhibitors. Cell Death Differ 8: 256-264.
65. McNeish IA, Bell S, McKay T, Tenev T, Marani M, et al. (2003) Expression of Smac/DIABLO in ovarian carcinoma cells induces apoptosis via a caspase-9-mediated pathway. Exp Cell Res 286: 186-198.
66. Chauhan D, Hideshima T, Rosen S, Reed JC, Kharbanda S, et al. (2001) Apaf-1/cytochrome c-independent and Smac-dependent induction of apoptosis in multiple myeloma (MM) cells. J Biol Chem 276: 24453-24456.
67. Oost TK, Sun C, Armstrong RC, Al-Assaad AS, Betz SF, et al. (2004) Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer. J Med Chem 47: 4417-4426.
68. Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, et al. (2004) A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science 305: 1471-1474.
69. Davoodi J, Lin L, Kelly J, Liston P, MacKenzie AE (2004) Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9. J Biol Chem 279: 40622-40628.
70. Pozarowski P, Huang X, Halicka DH, Lee B, Johnson G, et al. (2003) Interactions of fluorochrome-labeled caspase inhibitors with apoptotic cells: A caution in data interpretation. Cytometry A 55: 50-60.
71. Belloc F, Belaud-Rotureau MA, Lavignolle V, Bascans E, Braz-Pereira E, et al. (2000) Flow cytometry detection of caspase 3 activation in preapoptotic leukemic cells. Cytometry 40: 151-160.
72. Wright KM, Linhoff MW, Potts PR, Deshmukh M (2004) Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis. J Cell Biol 167: 303-313.
73. Potts PR, Singh S, Knezek M, Thompson CB, Deshmukh M (2003) Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis. J Cell Biol 163: 789-799.
74. Hu Y, Cherton-Horvat G, Dragowska V, Baird S, Korneluk RG, et al. (2003) Antisense oligonucleotides targeting XIAP induce apoptosis and enhance chemotherapeutic activity against human lung cancer cells in vitro and in vivo. Clin Cancer Res 9: 2826-2836.
75. Elowitz MB, Levine AJ, Siggia ED, Swain PS (2002) Stochastic gene expression in a single cell. Science 297: 1183-1186.
76. Bratton SB, Lewis J, Butterworth M, Duckett CS, Cohen GM (2002) XIAP inhibition of caspase-3 preserves its association with the Apaf-1 apoptosome and prevents CD95- and Bax-induced apoptosis. Cell Death Differ 9: 881-892.
77. Datta R, Oki E, Endo K, Biedermann V, Ren J, et al. (2000) XIAP regulates DNA damage-induced apoptosis downstream of caspase-9 cleavage. J Biol Chem 275: 31733-31738.
78. Kim JE, Tannenbaum SR (2004) Insulin regulates cleavage of procaspase-9 via binding of X chromosome-linked inhibitor of apoptosis protein in HT-29 cells. Cancer Res 64: 9070-9075.
79. Srinivasula SM, Datta P, Fan XJ, Fernandes-Alnemri T, Huang Z, et al. (2000) Molecular determinants of the caspase-promoting activity of Smac/DIABLO and its role in the death receptor pathway. J Biol Chem 275: 36152-36157.
80. Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C, et al. (2006) Mechanisms of cytochrome c release from mitochondria. Cell Death Differ 13: 1423-1433.
81. Clayton R, Clark JB, Sharpe M (2005) Cytochrome c release from rat brain mitochondria is proportional to the mitochondrial functional deficit: Implications for apoptosis and neurodegenerative disease. J Neurochem 92: 840-849.
82. Fortin A, Cregan SP, MacLaurin JG, Kushwaha N, Hickman ES, et al. (2001) APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death. J Cell Biol 155: 207-216.
83. Carson JP, Behnam M, Sutton JN, Du C, Wang X, et al. (2002) Smac is required for cytochrome c-induced apoptosis in prostate cancer LNCaP cells. Cancer Res 62: 18-23.
84. Schafer ZT, Parrish AB, Wright KM, Margolis SS, Marks JR, et al. (2006) Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells. Cancer Res 66: 2210-2218.
85. Huang Y, Rich RL, Myszka DG, Wu H (2003) Requirement of both the second and third BIR domains for the relief of X-linked inhibitor of apoptosis protein (XIAP)-mediated caspase inhibition by Smac. J Biol Chem 278: 49517-49522.
86. Uren RT, Dewson G, Bonzon C, Lithgow T, Newmeyer DD, et al. (2005) Mitochondrial release of pro-apoptotic proteins: Electrostatic interactions can hold cytochrome c but not Smac/DIABLO to mitochondrial membranes. J Biol Chem 280: 2266-2274.
87. Lim ML, Chen B, Beart PM, Nagley P (2006) Relative timing of redistribution of cytochrome c and Smac/DIABLO from mitochondria during apoptosis assessed by double immunocytochemistry on mammalian cells. Exp Cell Res 312: 1174-1184.
88. Zhou LL, Zhou LY, Luo KQ, Chang DC (2005) Smac/DIABLO and cytochrome c are released from mitochondria through a similar mechanism during UV-induced apoptosis. Apoptosis 10: 289-299.
89. Chipuk JE, Green DR (2005) Do inducers of apoptosis trigger caspase-independent cell death? Nat Rev Mol Cell Biol 6: 268-275.
90. Deveraux QL, Leo E, Stennicke HR, Welsh K, Salvesen GS, et al. (1999) Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J 18: 5242-5251.
91. Johnson DE, Gastman BR, Wieckowski E, Wang GQ, Amoscato A, et al. (2000) Inhibitor of apoptosis protein hILP undergoes caspase-mediated cleavage during T lymphocyte apoptosis. Cancer Res 60: 1818-1823.
92. Wagenknecht B, Glaser T, Naumann U, Kugler S, Isenmann S, et al. (1999) Expression and biological activity of X-linked inhibitor of apoptosis (XIAP) in human malignant glioma. Cell Death Differ 6: 370-376.
93. Herrera B, Fernandez M, Benito M, Fabregat I (2002) cIAP-1, but not XIAP, is cleaved by caspases during the apoptosis induced by TGF-beta in fetal rat hepatocytes. FEBS Lett 520: 93-96.
94. Widmann C, Gibson S, Johnson GL (1998) Caspase-dependent cleavage of signaling proteins during apoptosis. A turn-off mechanism for antiapoptotic signals. J Biol Chem 273: 7141-7147.
95. Dan HC, Sun M, Kaneko S, Feldman RI, Nicosia SV, et al. (2004) Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP). J Biol Chem 279: 5405-5412.
96. Holcik M, Sonenberg N (2005) Translational control in stress and apoptosis. Nat Rev Mol Cell Biol 6: 318-327.
97. Bowen C, Voeller HJ, Kikly K, Gelmann EP (1999) Synthesis of procaspases-3 and -7 during apoptosis in prostate cancer cells. Cell Death Differ 6: 394-401.
98. Casiano CA, Martin SJ, Green DR, Tan EM (1996) Selective cleavage of nuclear autoantigens during CD95 (Fas/APO-1)-mediated T cell apoptosis. J Exp Med 184: 765-770.
99. Ellerby HM, Martin SJ, Ellerby LM, Naiem SS, Rabizadeh S, et al. (1997) Establishment of a cell-free system of neuronal apoptosis: comparison of premitochondrial, mitochondrial, and postmitochondrial phases. J Neurosci 17: 6165-6178.
100. Tawa P, Hell K, Giroux A, Grimm E, Han Y, et al. (2004) Catalytic activity of caspase-3 is required for its degradation: Stabilization of the active complex by synthetic inhibitors. Cell Death Differ 11: 439-447.
101. Lademann U, Cain K, Gyrd-Hansen M, Brown D, Peters D, et al. (2003) Diarylurea compounds inhibit caspase activation by preventing the formation of the active 700-kilodalton apoptosome complex. Mol Cell Biol 23: 7829-7837.
102. Bentele M, Lavrik I, Ulrich M, Stosser S, Heermann DW, et al. (2004) Mathematical modeling reveals threshold mechanism in CD95-induced apoptosis. J Cell Biol 166: 839-851.
103. Fussenegger M, Bailey JE, Varner J (2000) A mathematical model of caspase function in apoptosis. Nat Biotechnol 18: 768-774.
104. Bagci EZ, Vodovotz Y, Billiar TR, Ermentrout GB, Bahar I (2006) Bistability in apoptosis: Roles of bax, bcl-2, and mitochondrial permeability transition pores. Biophys J 90: 1546-1559.
105. Stucki JW, Simon HU (2005) Mathematical modeling of the regulation of caspase-3 activation and degradation. J Theor Biol 234: 123-131.
106. Suzuki Y, Nakabayashi Y, Nakata K, Reed JC, Takahashi R (2001) X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and7 in distinct modes. J Biol Chem 276: 27058-27063.
107. Talanian RV, Quinlan C, Trautz S, Hackett MC, Mankovich JA, et al. (1997) Substrate specificities of caspase family proteases. J Biol Chem 272: 9677-9682.
108. Scott FL, Denault JB, Riedl SJ, Shin H, Renatus M, et al. (2005) XIAP inhibits caspase-3 and7 using two binding sites: Evolutionarily conserved mechanism of IAPs. EMBO J 24: 645-655.
109. Yin Q, Park HH, Chung JY, Lin SC, Lo YC, et al. (2006) Caspase-9 holoenzyme is a specific and optimal procaspase-3 processing machine. Mol Cell 22: 259-268.