Proapoptotic multidomain Bcl-2/Bax-family proteins: Mechanisms, physiological roles, and therapeutic opportunities

Cell Death and Differentiation

Volumn 13, Issue 8, 2006, Pages 1378-1386

  Reed, J C ^a  

^a BURNHAM INSTITUTE   (United States)

Author keywords

Bak; Bax; Bcl 2; Bok; Cell death

Indexed keywords

ANTINEOPLASTIC AGENT; BH3 PROTEIN; BIM PROTEIN; CALCIUM ION; CELL NUCLEUS RECEPTOR; DNA DEPENDENT PROTEIN KINASE; HISTONE DEACETYLASE INHIBITOR; HUMANIN; PIPERAZINE DERIVATIVE; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN BID; PROTEIN BIF 1; PROTEIN BOK; PROTEIN DERIVATIVE; PROTEIN INHIBITOR; PROTEIN P53; UNCLASSIFIED DRUG; VOLTAGE GATED CHANNEL FORMING PROTEIN;

AMINO ACID SEQUENCE; APOPTOSIS; BIOCHEMISTRY; CALCIUM HOMEOSTASIS; CANCER INHIBITION; CELL DEATH; CELLULAR DISTRIBUTION; ENDOPLASMIC RETICULUM; HOMEOSTASIS; MAMMAL; MEDICAL RESEARCH; MITOCHONDRIAL MEMBRANE; NERVE CELL NECROSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REGULATORY MECHANISM; REVIEW;

ANIMALS; APOPTOSIS; ENDOPLASMIC RETICULUM; HUMANS; MITOCHONDRIA; MODELS, BIOLOGICAL; PROTO-ONCOGENE PROTEINS C-BCL-2;

MAMMALIA;

EID: 33745957572     PISSN: 13509047     EISSN: 14765403     Source Type: Journal    
DOI: 10.1038/sj.cdd.4401975     Document Type: Review

References (108)

1. Oltvai Z, Milliman C and Korsmeyer S (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74: 609-519.
2. Boise L, Gonzalez-Garcia M, Postema C, Ding L, Lindsten T, Turks L, Turka L, Mao X, Nunez G and Thompson C (1993) Bcl-x, a Bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 74: 597-608.
3. Yin XM, Oltvai ZN and Korsmeyer SJ (1994) BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodmerization with bax. Nature 369: 321-333.
4. Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ and Schlesinger PH (2000) Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ. 7: 1166-1173.
5. Strasser A (2005) The role of BH3-only proteins in the immune system. Nat. Rev. Immunol. 5: 189-200.
6. Sato T, Hanada M, Bodrug S, Irie S, Iwama N, Boise LH, Thompson CB, Golemis E, Fong L, Wang H-G and Reed JC (1994) Interactions among members of the Bcl-2 protein family analyzed with a yeast two-hybrid system. Proc. Natl. Acad. Sci. USA 91: 9238-9242.
7. Hanada M, Aime-Sempe C, Sato T and Reed JC (1995) Structure-function analysis of Bcl-2 protein. Identification of conserved domains important for homodimerization with Bcl-2 and heterodimerization with Bax. J. Biol. Chem. 270: 11962-11989.
8. Jurgensmeier JM, Krajewski S, Armstrong R, Wilson GM, Oltersdorf T, Fritz LC, Reed JC and Ottilie S (1997) Bax- and Bak-induced cell death in the fission yeast Schizosaccharomyces pombe. Mol. Biol. Cell. 8: 325-339.
9. Kawai-Yamada M, Jin L, Yoshinaga K, Hirata A and Uchimiya H (2001) Mammalian Bax-induced plant cell death can be down-regulated by overexpression of Arabidopsis Bax Inhibitor-1 (AtBI-1). Proc. Natl. Acad. Sci. USA 98: 12295-12300.
10. Huang DC and Strasser A (2000) BH3-only proteins-essential initiators of apoptotic cell death. Cell 103: 839-842.
11. Reed JC, Doctor KS and Godzik A (2004) The domains of apoptosis: A genomics perspective. Sci. STKE 2004: RE9.
12. Suzuki M, Youle RJ and Tjandra N (2000) Structure of bax: Coregulation of dimer formation and intracellular localization. Cell 103: 645-654.
13. Chou J, Li H, Salvesen G, Yuan J and Wagner G (1999) Solution structure of BID, an intracellular amplifier of apoptotic signaling. Cell 96: 615-624.
14. Knudson CM, Tung KSK, Tourtellotte WG, Brown GAJ and Korsmeyer SJ (1995) Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 270: 96-99.
15. White F, Keller-Peck C, Knudson C, Korsmeyer S and Snider W (1998) Widespread elimination of naturally occuring neuronal death in Bax-deficient mice. J. Neurosci. 18: 1428-1439.
16. Shibata MA, Liu ML, Knudson MC, Shibata E, Yoshidome K, Bandey T, Korsmeyer SJ and Green JE. (1999) Haploid loss of bax leads to accelerated mammary tumor development in C3(1)/SV40-TAg transgenic mice: reduction in protective apoptotic response at the preneoplastic stage. EMBO J. 18: 2692-2701.
17. Knudson CM, Johnson GM, Lin Y and Korsmeyer SJ (2001) Bax accelerates tumorigenesis in p53-deficient mice. Cancer Res. 61: 659-665.
18. Eischen CM, Rehg JE, Korsmeyer SJ and Cleveland JL (2002) Loss of Bax alters tumor spectrum and tumor numbers in ARF-deficient mice. Cancer Res. 62: 2184-2191.
19. Deckwerth TL, Elliott JL, Knudson CM, Johnson JEM, Snider WD and Korsmeyer SJ (1996) BAX is required for neuronal death after trophic factor deprivation and during development. Neuron 17: 401-411.
20. Gillardon F, Zimmermann M, Uhlmann E, Krajewski S, Reed JC and Klimaschewski L (1996) Antisense oligodeoxynucleotides to bax mRNA promote survival of rat sympathetic neurons in culture. J. Neurosci. Res. 43: 726-734.
21. Miyashita T and Reed JC (1995) Tumor suppressor p53 is a direct transcriptional activator of human Bax gene. Cell 80: 293-299.
22. Sakhi S, Bruce A, Sun N, Tocco G, Baudry M and Schreiber SS (1994) p53 induction is associated with neuronal damage in the central nervous system. Proc. Natl. Acad. Sci. USA 91: 7525-7529.
23. Manev H, Kharlamov A and Armstrong DM (1994) Photochemical brain injury in rats triggers DNA fragmentation, p53 and HSP72. Neuroreport 5: 2661-2664.
24. Morrison RS, Wenzel HJ, Kinoshita Y, Robbins CA, Donehower LA and Schwartzkroin PA (1996) Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death. J. Neurosci. 16: 1337-1345.
25. Wood KA and Youle RJ (1995) The role of free readicals and p53 in neuron apoptosis in vivo. J. Neurosci. 15: 5851-5857.
26. Krajewski S, Mai JK, Krajewska M, Sikorska M, Mossakowski MJ and Reed JC (1995) Upregulation of Bax protein levels in neurons following cerebral ischemia. J. Neurosci. 15: 6364-6376.
27. Hara A, Iwai T, Niwa M, Uematsu T, Yoshimi N, Tanaka T and Mori H (1996) Immunohistochemical detection of Bax and Bcl-2 proteins in gerbil hippocampus following transient forebrain ischemia. Brain Res. 711: 249-253.
28. Krajewska M, Zapata JM, Meinhold-Heerlein I, Hedayat H, Monks A, Bettendorf H and Krajewski S (2002) Expression of Bcl-2 family member Bid in normal and malignant tissues. Neoplasia 4: 129-140.
29. Gillardon F, Lenz C, Waschke KF, Krajewski S, Reed JC, Zimmerman M and Kuschinsky W (1996) Altered expression of Bcl-2, Bcl-X, BAX, and c-Fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats. Mol. Brain Res. 40: 254-260.
30. Gibson ME, Han BH, Choi J, Knudson CM, Korsmeyer SJ, Parsadanian M and Holtzman DM (2001) BAX contributes to apoptotic-like death following neonatal hypoxia-ischemia: Evidence for distinct apoptosis pathways. Mol. Med. 7: 644-655.
31. Hughes PE, Alexi T, Yoshida T, Schreiber SS and Knusel B (1996) Excitotoxic lesion on rat brain with quinolinic acid induces expression of p53 messenger RNA and protein and p53-inducible genes BAX and GADD-45 in brain areas showing DNA fragmentation. Neuroscience 74: 1143-1160.
32. Gillardon F, Wickert H and Zimmerman M (1995) Up-regulation of bax and down-regulation of bcl-2 is associated with kainate-induced apoptosis in mouse brain. Neurosci. Lett. 192: 85-88.
33. Paradis E, Douillard H, Koutroumanis M, Goodyer C and LeBlanc A (1996) Amyloid β peptide of Alzheimer's disease downregulates Bcl-2 and upregulates Bax expression in human neurons. J. Neurosci. 16: 7533-7539.
34. Hassouna I, Wickert H, Zimmerman M and Gillardon F (1996) Increase in bax expression in substantia nigra following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment of mice. Neurosci. Lett. 204: 85-88.
35. Gillardon F, Klimaschewski L, Wickert H, Krajewski S, Reed JC and Zimmermann M (1996) Expression pattern of candidate cell death effector proteins Bax, Bcl-2, Bcl-X, and c-Jun in sensory and motor neurons following sciatic nerve transection in the rat. Brain Res. 739: 244-250.
36. Estus S, Zaks WJ, Freeman RS, Gruda M, Bravo R and Johnson Jr EM (1994) Altered gene expression in neurons during programmed cell death: identification of c-jun as necessary for neuronal apoptosis. J. Cell Biol. 127: 1717-1727.
37. Mu X, He J, Anderson DW, Trojanowski JQ and Springer JE (1996) Altered expression of bcl-2 and bax mRNA in amyotrophic lateral sclerosis spinal cord motor neurons. Ann. Neurol. 40: 379-386.
38. Vukosavic S, Dubois-Dauphin M, Romero N and Przedborski S (1999) Bax and Bcl-2 interaction in a transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem. 73: 2460-2468.
39. Krajewski S, James H, Ross J, Blumberg B, Epstein L, Gendelman H, Dewhurst S, Sharer L, Reed J and Gelbard H (1997) Expression of pro- and anti-apoptosis gene products in brains from paediatric patients with HIV-1 encephalitis. Neuropathol. Appl. Neurobiol. 23: 242-253.
40. Misao J, Hayakawa Y, Ohno M, Kato S, Fujiwara T and Fujiwara H (1996) Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction. Circulation 94: 1506-1512.
41. Russell Hr, Lee Y, Miller HL, Zhao J and McKinnon PJ (2002) Murine ovarian development is not affected by inactivation of the Bcl-2 family member diva. Mol. Cell. Biol. 22: 6866-6870.
42. Lindsten T, Ross AJ, King A, Zong W, 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 and 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.
43. Hsu S, Kaipa A, McGee E, Lomeli M and Hsueh A (1997) Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members. Proc. Natl. Acad. Sci. USA 94: 12401-12406.
44. Lee R, Chen J, Matthews CP, McDougall JK and Neiman PE (2001) Characterization of NR13-related human cell death regulator, Boo/Diva, in normal and cancer tissues. Biochim. Biophys. Acta 1520: 187-194.
45. Krajewski S, Krajewska M and Reed JC (1996) Immunohistochemical analysis of in vivo patterns of Bak expression, a pro-apoptotic member of the Bcl-2 protein family. Cancer Res. 56: 2849-2855.
46. Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB and Korsmeyer SJ (2001) Proapoptotic BAX and BAK: A requisite gateway to mitochondrial dysfunction and death. Science 292: 727-730.
47. Hahn P, Lindsten T, Lyubarsky A, Ying GS, Pugh Jr EN, Thompson CB and Dunaief JL. (2004) Deficiency of Bax and Bak protects photoreceptors from light damage in vivo. Cell Death Differ. 11: 1192-1197.
48. Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB and Tsujimoto Y (2004) Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat. Cell. Biol. 6: 1221-1228.
49. Martinou J-C and Green DR (2001) Breaking the mitochondrial barrier. Nat. Rev. Mol. Cell. Biol. 2: 63-67.
50. Waterhouse NJ, Ricci JE and Green DR (2002) And all of a sudden it's over: Mitochondrial outer-membrane permeabilization in apoptosis. Biochimie 84: 113-121.
51. Cheng EH-Y, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T and Korsmeyer SJ (2001) BCL2, BCL-XL sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol. Cell. 8: 705-711.
52. Marzo I, Brenner C, Zamzami N, Jürgensmeier JM, Susin SA, Vieira HLA, Prevost M-C, Xie Z, Matsuyama S, Reed JC and Kroemer G (1998) Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science 281: 2027-2031.
53. 1-ATPase proton-pump is required for function of pro-apoptotic protein bax in yeast and mammallan cells. Mol. Cell. 1: 327-336.
54. Milanesi E, Costantini P, Gambalunga A, Colonna R, Petronilli V, Cabrelle A, Semenzato G, Cesura AM, Pinard E and Bernardi P (2006) The mitochondrial effects of small organic ligands of BCL-2. Sensitization of BCL-2-overexpressing cells to apoptosis by a pyrimidine-2,4,6-trione derivative. J. Biol. Chem. 281: 10066-10072.
55. Bernardi P, Krauskopf A, Basson E, Petronilli V, Blachly-Dyson E, Di Lisa F and Forte MA (2006) The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J. 273: 2077-2099.
56. Reed JC and Green DR (2002) Remodeling for demolition: Changes in mitochondrial ultrastructure during apoptosis. Mol. Cell. 9: 1-3.
57. Nechushtan A, Smith CL, Lamensdorf I, Yoon S-H and Youle RJ (2001) Bax and Bak coalesce into novel mitochondria-associated clusters during apoptosis. J. Cell. Biol. 153: 1265-1276.
58. Szabadkai G, Simoni AM, Chami M, Wieckowski MR, Youle RJ and Rizzuto R (2004) Drp-1-dependent division of the mitochondrial network blocks intraorganellar Ca2+ waves and protects against Ca2+-mediated apoptosis. Mol. Cell. 16: 59-68.
59. Inohara N, Gourley TS, Carrio R, Muniz M, Merino J, Garcia I, Koseki T, Hu Y, Chen S and Nunez G (1998) Diva, a Bcl-2 homologue that binds directly to Apaf-1 and induces BH3-independent cell death. J. Biol. Chem. 273: 32479-32486.
60. Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T and Korsmeyer SJ (2005) Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA 102: 105-110.
61. Nutt LK, Pataer A, Pahler J, Fang B, Roth J, McConkey DJ and Swisher SG (2002) Bax and Bak promote apoptosis by modulating endoplasmic reticular and mitochondrial Ca2+ stores. J. Biol. Chem. 277: 9219-9225.
62. Demaurex N and Distelhorst C (2003) Apoptosis-the calcium connection. Science 300: 65-67.
63. Chami M, Prandini A, Campanella M, Pinton P, Szabadkai G, Reed JC and Rizzuto R (2004) Bcl-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on their putative pore-forming region. J. Biol. Chem. 279: 54581-54589.
64. White C, Li C, Yang J, Petrenko NB, Madesh M, Thompson CB and Foskett JK (2005) The endoplasmic reticulum gateway to apoptosis by Bcl-X(L) modulation of the InsP3R. Nat. Cell. Biol. 7: 1021-1028.
65. Chen R, Valencia I, Zhong F, McColl KS, Roderick HL, Bootman MD, Berridge MJ, Conway SJ, Holmes AB, Mignery GA, Velez P and Distelhorst CW (2004) Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate. J. Cell. Biol. 166: 193-203.
66. Kuo TH, Kim HR, Zhu L, Yu Y, Lin HM and Tsang W (1998) Modulation of endoplasmic reticulum calcium pump by Bcl-2. Oncogene 17: 1903-1910.
67. Baffy G, Miyashita T, Williamson JR and Reed JC (1993) Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production. J. Biol. Chem. 268: 6511-6519.
68. Palmer AE, Jin C, Reed JC and Tsien RY (2004) Bcl-2-mediated alterations in endoplasmic reticulum Ca2+ analyzed with an improved genetically encoded fluorescent sensor. Proc. Natl. Acad. Sci. USA 101: 17404-17409.
69. Wolter KG, Hsu YT, Smith CL, Nechushtan A, Xi XG and Youle RJ (1997) Movement of bax from the cytosol to mitochondria during apoptosis. J. Cell. Biol. 139: 1281-1292.
70. Nechushtan A, Smith C, Hsu Y-T and Youle R (1999) Conformation of the Bax C-terminus regulates subcellular location and cell death. EMBO J. 18: 2330-2341.
71. Gross A, McDonnell JM and Korsmeyer SJ (1999) BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13: 1899-1911.
72. Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R, Green DR and Newmeyer DD (2002) Bid, bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 111: 331-342.
73. Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A, Ashiya M, Thompson CB and Korsmeyer SJ (2000) tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev. 14: 2060-2071.
74. Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S and Korsmeyer SJ (2002) Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2: 183-192.
75. Wang K, Yin W-M, Chao DT, Milliman CL and Korsmeyer SJ (1996) BID: A novel BH3 domain-only death agonist. Genes Dev. 10: 2859-2869.
76. Strasser A, Puthalakath H, Bouillet P, Huang DC, O'Connor L, O'Reilly LA, Cullen L, Cory S and Adams JM (2000) The role of bim, a proapoptotic BH3-only member of the Bcl-2 family in cell-death control. Ann. NY Acad Sci. 917: 541-548.
77. Puthalakath H, Huang D, O'Reilly L, King S and Strasser A (1999) The proapoptotic activity of the Bcl-2 family member bim is regulated by interaction with the dynein motor complex. Mol. Cell. 3: 287-296.
78. Zhu Y, Swanson BJ, Wang M, Hildeman DA, Schaefer BC, Liu X, Suzuki H, Mihara K, Kappler J and Marrack P (2004) Constitutive association of the proapoptotic protein Bim with Bcl-related proteins on mitochondria in T cells. Proc. Natl. Acad. Sci. USA 101: 7681-7686.
79. Cheng E, Clem R, Ravi R, Kirsch D, Kastan M, Bedi A, Ueno K and Hardwick J (1997) Conversion of Bcl-2 to a Bax-like death effector by caspases. Science 278: 1966-1968.
80. Lin B, Kolluri SK, Lin F, Liu W, Han Y-H, Cao X, Dawson MI, Reed JC and Zhang X-K (2004) Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor TR3/NGFI-B/Nur77. Cell 116: 527-540.
81. Zha H and Reed JC (1997) Heterodimerization-independent functions of cell death regulatory proteins Bax and Bcl-2 in yeast and mammalian cells. J. Biol. Chem. 272: 31482-31488.
82. Cuddeback SM, Yamaguchi H, Komatsu K, Miyashita T, Yamada M, Wu C, Singh S and Wang HG (2001) Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax. J. Biol. Chem. 276: 23.
83. Takahashi Y, Karbowski M, Yamaguchi H, Kazi A, Wu J, Sebti SM, Youle RJ and Wang HG (2005) Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis. Mol. Cell. Biol. 25: 9369-9382.
84. Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M and Green DR (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303: 1010-1014.
85. Ohtsuka T, Ryu H, Minamishima YA, Macip S, Sagara J, Nakayama KI, Aaronson SA and Lee SW (2004) ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis pathway. Nat. Cell. Biol. 6: 121-128.
86. Simonian PL, Grillot DAM, Merino R and Nunez G (1996) Bax can antagonize Bcl-XL during etoposide and cisplatin-induced cell death independently of its heterodimerizaton with Bcl-XL. J. Biol. Chem. 271: 22764-22772.
87. Danial NN and Korsmeyer SJ (2004) Cell death: Critical control points. Cell 116: 205-219.
88. Sawada M, Sun W, Hayes P, Leskov K, Boothman DA and Matsuyama S (2003) Ku70 suppresses the apoptotic translocation of Bax to mitochondria. Nat. Cell. Biol. 5: 320-329.
89. Sawada M, Hayes P and Matsuyama S (2003) Cytoprotective membrane-permeable peptides designed from the Bax-binding domain of Ku70. Nat Cell. Biol. 5: 352-357.
90. Yoo CB and Jones PA (2006) Epigenetic therapy of cancer: Past, present and future. Nat. Rev. Drug Discov. 5: 37-50.
91. Guo B, Zhai D, Cabezas E, Welsh K, Nouraini S, Satterthwait AC and Reed JC (2003) Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature 423: 456-461.
92. Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Kolde T, Tsuji S, Lang J, Kurokawa K and Nishimoto I (2001) A resuce factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ. Proc. Natl. Acad. Sci. USA 98: 6336-6341.
93. Zhai D, Luciano F, Zhu X, Guo B, Satterthwait A and Reed JC (2005) Humanin binds and nullifies Bid activity by blocking its activation of Bax and Bak. J. Biol. Chem. 280: 15815-15824.
94. Luciano F, Zhai D, Zhu X, Bailly-Maitre B, Ricci JE, Satterthwait AC and Reed JC (2005) Cytoprotective peptide Humanin binds and inhibits pro-apoptotic Bcl-2/Bax-family protein BimEL. J. Biol. Chem. 280: 15825-15835.
95. Cheng EH, Sheiko TV, Fisher JK, Craigen WJ and Korsmeyer SJ (2003) VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science 301: 513-517.
96. Chandra D, Choy G, Daniel PT and Tang DG (2005) Bax-dependent regulation of Bak by voltage-dependent anion channel 2. J. Biol. Chem. 280: 19051-19061.
97. Debatin KM, Poncet D and Kroemer G (2002) Chemotherapy: Targeting the mitochondrial cell death pathway. Oncogene 21: 8786-8803.
98. Tsujimoto Y (2003) Cell death regulation by the Bcl-2 protein family in the mitochondria. J. Cell. Physiol. 195: 158-167.
99. Rostovtseva TK, Antonsson B, Suzuki M, Youle RJ, Colombini M and Bezrukov SM (2004) Bid, but not Bax, regulates VDAC channels. J. Biol. Chem. 279: 13575-13583.
100. Zalk R, Israelson A, Garty ES, Azoulay-Zohar H and Shoshan-Barmatz V (2005) Oligomeric states of the voltage-dependent anion channel and cytochrome c release from mitochondria. Biochem J. 386: 73-83.
101. Reed JC and Pellecchia M (2005) Apoptosis-based Therapies for Hematological Malignancies. Blood 106: 408-418.
102. Rampino N, Yamamoto H, Ionov Y, Li Y, Sawai H, Reed JC and Perucho M (1997) Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 275: 967-969.
103. Kondo S, Shinomura Y, Miyazaki Y, Kiyohara T, Tsutsui S, Kitamura S, Nagasawa Y, Nakahara M, Kanayama S and Matsuyama Y (2000) Mutations of the bak gene in human gastric and colorectal cancers. Cancer Res. 60: 4328-4330.
104. Xiang J, Gomez-Navarro J, Arafat W, Liu B, Barker SD, Alvarez RD, Siegal GP and Curiel DT (2000) Pro-apoptotic treatment with an adenovirus encoding Bax enhances the effect of chemotherapy in ovarian cancer. J. Gene Med. 2: 97-106.
105. Bombrun A, Gerber P, Casi G, Terradillos O, Antonsson B and Halazy S (2003) 3,6-dibromocarbazole piperazine derivatives of 2-propanol as first inhibitors of cytochrome c release via Bax channel modulation. J. Med. Chem. 46: 4365-4368.
106. Becattini B, Sareth S, Zhai D, Crowell K, Leone M, Reed JC and Pellecchia M (2004) Targeting apoptosis via chemical design: Inhibition of Bid-induced cell-death by small organic molecules. Chem. Biol. 11: 1107-1117.
107. Plesnila N, Zinkel S, Le DA, Amin-Hanjani S, Wu Y, Qiu J, Chiarugi A, Thomas SS, Kohane DS, Korsmeyer SJ and Moskowitz MA (2001) BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia. Proc. Natl. Acad. Sci. USA 98: 15318-15323.
108. Yin X-M, Wang K, Gross A, Klocke B, Roth KA and Korsmeyer SJ (1999) Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature 400: 886-891.