Mechanisms controlling cellular suicide: Role of Bcl-2 and caspases

Cellular and Molecular Life Sciences

Volumn 54, Issue 5, 1998, Pages 427-445

  Allen, R T ^a   Cluck, M W ^a   Agrawal, D K ^a  

^a CREIGHTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Apoptosis; Apoptosis protease activating factor; Bcl 2; Caenorhabditis elegans; Caspases; Fas; Interleukin 1 converting enzyme proteases; Retinoblastoma; Smooth muscle cell

Indexed keywords

PHOSPHOTRANSFERASE; PROTEIN BCL 2; RAF PROTEIN;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; APOPTOSIS; CANCER; CELL DEATH; CYTOSOL; DEGENERATIVE DISEASE; HUMAN; PROTO ONCOGENE; REVIEW; VASCULAR DISEASE;

ANIMALS; APOPTOSIS; CYSTEINE ENDOPEPTIDASES; HUMANS; PROTO-ONCOGENE PROTEINS C-BCL-2;

EID: 0031809920     PISSN: 1420682X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s000180050171     Document Type: Review

References (200)

1. Kerr J. F. R., Winterford C. M. and Harmon B. V. (1994) Apoptosis: its significance in cancer and cancer therapy. Cancer 73: 2013-2026
2. Thompson C. B. (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267: 1456-1462
3. Oyaizu N. and Pahwa S. (1995) Role of apoptosis in HIV disease pathogenesis. J. Clin. Immunol. 15: 217-231
4. Shi B., Girolami U. D., He J., Wang S., Lorenzo A., Busciglio J. et al. (1996) Apoptosis induced by HIV infection of the central nervous system. J. Clin. Invest. 98: 1979-1990
5. Isner J. M., Kearney M., Bortman S., Passeri J. (1995) Apoptosis in human atherosclerosis and restenosis. Circulation 91: 2703-2711
6. Han D. K. M., Haudenschild C. C., Hong M. K., Tinkle B. T., Leon M. B. and Liau G. (1995) Evidence for apoptosis in human atherocenesis and in a rat vascular injury model. Am. J. Pathol. 147: 267-277
7. Vaux D. L., Cory S. and Adams T. M. (1988) Bcl-2 promotes survival of haemopoietic cells and cooperates with c-myc to immortalize pre-B cells. Nature 335: 440-442
8. Hockenbery D., Nunez G., Milliman C., Schreitber R. D. and Korsmeyer S. (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348: 334-336
9. Boise L. H., Gonzalez-Garcia M., Postema C. E., Ding L., Lindsten T., Turka L. A. et al. (1993) bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptosis. Cell 74: 597-608
10. Choi S. S., Park I., Yun J. W., Sung Y. C., Hong S. and Shin H. (1995) A novel Bcl-2 related gene, Bfl-1, is overexpressed in stomach cancer and preferentially expressed in bone marrow. Oncogene 11: 1693-1698
11. D'Sa-Eipper C., Subramanian T. and Chinnadurai G. (1996) bfl-1, a bcl-2 homologue, suppresses p53-induced apoptosis and exhibits potent cooperative transforming activity. Cancer Res 56: 3879-3882
12. Kozopas K. M., Yang T., Buchan H. L., Zhou P. and Craig R. W. (1993) MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL-2. Proc. Natl. Acad. Sci. USA 90: 3516-3520
13. Reynolds J. E., Yang T., Qian L. P., Jenkinson J. D., Zhou P., Eastman A. et al. (1994) MCL1, a member of the bcl-2 family, delays apoptosis induced by c-myc overexpression in Chinese hamster ovary cells. Cancer Res. 54: 6348-6352
14. Lin E. Y., Orlofsky A., Berger M. S. and Pryustowsky M. B. (1993) Characterization of A1, a novel hemopoietic-specific early response gene with sequence similarity to bcl-2. J Immunol 151: 1979-1988
15. Hengartner M. O. and Horvitz H. R. (1994) C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell 76: 665-676
16. White E., Sabbatini P., Debbas M., Wold W. S. M., Kusher D. I. and Gooding L. (1992) The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor α. Mol. Cell Biol. 12: 2570-2580
17. Farrow S. N., White J. H. M., Martinou I., Raven T., Pun K.-T., Grinham C. J. et al. (1995) Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K. Nature 374: 731-733
18. Han J. P., Sabbatini P., Perez D., Rao L., Modha D. and White E. (1996) The E1B 19K protein blocks apoptosis by interacting with and inhibiting the p53-inducible and death-promoting Bax protein. Genes Dev. 10: 461-477
19. Cleary M. L., Smith S. D. and Sklar J. (1986) Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 47: 19-28
20. Henderson S., Huen D., Rowe M., Dawson C., Johnson G. and Rickinson A. (1993) Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc. Natl. Acad. Sci. USA 90: 8479-8483
21. Neilan J. G., Lu Z., Afonzo C. L., Kutish G. F., Sussman M. D. and Rock D. L. (1993) An African swine fever virus gene with similarity to the proto-oncogene bcl-2 and the Epstein-Barr virus gene BHRF1. J. Virol. 67: 4391-4394
22. Smith C. A. (1995) A novel viral homologue of Bcl-2 and Ced-9. Trends Cell Biol. 5: 344
23. Russo J. J., Bohenzky R. A., Chien M.-C., Chen J., Yan M., Maddalena D. et al. (1996) Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc. Natl. Acad. Sci. USA 93: 14862-14867
24. Oltvai Z. N., Milliman C. L. and Korsmeyer S. J. (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74: 609-619
25. Chittenden T., Harrington E. A., O'Conner R., Flemington C. Lutz R. J., Evan G. I. et al. (1995) Induction of apoptosis by the Bcl-2 homologue Bak. Nature 374: 733-736
26. Kiefer M. C., Brauer M. J., Powers V. C., Wu J. J., Umansky S. R., Tomei L. D. et al. (1995) Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak. Nature 374: 736-739
27. Yang E., Zha J., Jockel J., Boise L. H., Thompson C. B. and Korsmeyer S. J. (1995) Bad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces Bax and promotes cell death. Cell 80: 285-291
28. Boyd J. M., Gallo G. J., Elangovan B., Houghton A. B., Malstrom S., Avery B. J. et al. (1995) Bik1, a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival promoting proteins. Oncogene 11: 1921-1927
29. Han J., Sabbatini P. and White E. (1996) Induction of apoptosis by human Nbk/Bik, a BH3 containing E1B 19K interacting prolein. Mol. Cell Biol. 16: 5857-5864
30. L. EMBO J. 16: 101-109
31. Wang K., Yin X.-M., Chao D. T., Milliman C. L. and Korsmeyer S. J. (996) BID: a novel BH3 domain-only death agonist. Genes Dev. 10: 2859-2869
32. Korsmeyer S. J. (1992) Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood 359: 554-556
33. Zhu W., Cowie A., Wasfy G. W., Penn L. Z., Leber B. and Andrews D. W. (1996) Bcl-2 mutants with restricted subcellular location reveal spatially distinct pathways for apoptosis in different cell types. EMBO J. 15: 4130-4141
34. Nunez G., London L., Hockenbery D., Alexander M., McKearn J. P. and Korsmeyer S. J. (1990) Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. J. Immunol. 144: 3602-3610
35. Garcia I., Martinou I., Tsujimoto Y. and Martinou J.-C. (1992) Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene. Science 258: 302-304
36. Sentman C. L., Shutter J. R., Hockenbery D., Kanagawa O. and Korsmeyer S. J. (1994) bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell 67: 879-888
37. Cuende E., Ales-Martinez J. E., Ding L., Gonzalez-Garcia M., Martinez C. and Nunez G. (1993) Programmed cell death by bcl-2-dependent and independent mechanisms in B lymphoma cells. EMBO J. 12: 1555-1560
38. Dole M. G., Nunez G., Merchant A. K., Maybaum J., Rode C. K., Bloch C. A. et al. (1994) Bcl-2 inhibits chemotherapy-induced apoptosis in neuroblastoma. Cancer Res 54: 3253-3259
39. Novack D. V. and Korsmeyer S. J. (1994) Bcl-2 protein expression during murine development. Am. J. Pathol. 145: 61-73
40. Hockenbery D. M., Zutter M., Hickey W., Nahm M. and Korsmeyer S. J. (1991) Bcl-2 protein is topographically restricted in tissues characterized by apoptotic death. Proc. Natl. Acad. Sci. USA 88: 6961-6965
41. McDonnell T. J. and Korsmeyer S. J. (1991) Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14:18). Nature 349: 254-256
42. Askew D. S., Ashmun R. A., Simmons B. C. and Cleveland J. L. (1991) Constitutive c-myc expression in an I. L.-3-dependent cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene 6: 1915-1922
43. Bissonette R. P., Echeverri F., Mahboubi A. and Green D. R. (1992) Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature 359: 552-554
44. Fanidi A., Harrington E. A. and Evan G. I. (1992) Cooperative interaction between c-myc and bcl-2 proto-oncogenes. Nature 359: 554-556
45. Nunez G., Seto M., Seremetis S., Ferrero D., Grignani F., Korsmeyer S. J. et al. (1989) Growth-and tumor-promoting effects of deregulated BCL-2 in human B-lymphoblastoid cells. Proc. Natl. Acad. Sci. USA 86: 4589-4593
46. Reed J. C., Halder S., Croce C. M. and Cuddy M. P. (1990) Complementation by BCL2 and C-HA-RAS oncogenes in malignant transformation of rat embryo fibroblasts. Mol. Cell Biol. 10: 4370-4374
47. Rampino N., Yamamoto H., Ionov Y., Li Y., Sawai H., Reed J. C. et al. (1997) Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 275: 967-969
48. Vaux D. L., Aguila H. L. and Weissman I. L. (1992) Bcl-2 prevents death of factor-deprived cells but fails to prevent apoptosis in targets of cell mediated killing. Int. Immunol. 4: 821-824
49. Sentman C. L., Shutter J. R., Hockenbery D., Kanagawa O. and Korsmeyer S. J. (1991) Bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell 67: 879
50. Sato T., Hanada M., Bodrug S., Irie S., Iwama N., Boise L. H. et al. (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
51. Sedlak T. W., Oltvai Z. N., Yang E., Wang K., Boise L. H., Thompson C. B. et al. (1995) Multiple Bcl-2 family members demonstrate selective dimerizations with Bax. Proc. Natl. Acad. Sci. USA 92: 7834-7838
52. Knudson C. M., Tung K., S., Tourtellotte W. G., Brown G. and Korsmeyer S. J. (1945) Bax-deficient mice demonstrate lymphoid hyperplasia but male germ cell death. Science 270: 96-99
53. White E. (1996) Life, death and the pursuit of apoptosis. Genes Dev. 10: 1-15
54. Chittenden T., Flemmington C., Houghton A. B., Ebb R. G., Gallo G. J., Elangovan B. et al. (1995) A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. EMBO J. 14: 5589-5596
55. Zha H., Aime-Sempe C., Sato T. and Reed J. C. (1996) Proapoptotic protein Bax heterodimerizes with Bcl-2 and homodimerizes with Bax via a novel domain (BH3) distinct from BH1 and BH2. J. Biol. Chem. 271: 7440-7444
56. Hunter J. and Parslow T. G. (1996) A peptide sequence from Bax that converts Bcl-2 into an activator of apoptosis. J. Biol. Chem. 271: 8521-8524
57. L-Bak peptide complex: recognition between regulators of apoptosis. Science 275: 983-986
58. Hockenbery D. M., Oltvai Z. N., Yin X.-M., Milliman C. L. and Korsmeyer S. J. (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75: 241-251
59. Jacobson M. D. and Raff M. C. (1995) Programmed cell death and Bcl-2 protection in very low oxygen. Nature 374: 814-816
60. Jacobson M. D., Burne J. F., King M. P., Miyashita T., Reed J. C. and Raff M. C. (1993) Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA. Nature 361: 365-369
61. Baffy G., Miyashita T., Williamson J. R. and Reed J. C. (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
62. 2+ fluxes. Proc. Natl. Acad. Sci. USA 91: 6569-6573
63. Zamzami N., Marchetti P., Castedo M., Zanin C., Vayssiere J.-L., Petit P. X. et al. (1995) Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J. Exp. Med. 181: 1661-1672
64. L, an inhibitor of programmed cell death. Nature 381: 335-341
65. Minn A. J., Velez P., Schendel S. L., Liang H., Muchmore S. W., Fesik S. W. et al. Bcl-xL forms an ion channel in synthetic lipid membranes. Nature 385: 353-357
66. London L. (1992) Diptheria toxin: membrane interaction and membrane translocation. Biochim. Biophys. Acta. 1113: 25-51
67. Liu X., Kim C. N., Yang J., Jemmerson R. and Wang X. (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86: 147-157
68. Martin S. J. and Green D. R. (1995) Protease activation during apoptosis: death by a thousand cuts? Cell 82: 349-352
69. Yang J., Liu X., Bhalla K., Kim C. N., Ibrado A. M., Cai J. et al. (1997) Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275: 1129-1132
70. Kluck R. M., Bossy-Wetzel E., Green D. R. and Newmeyer D. D. (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275:1132-1136
71. Jacobson M. D. (1997) Apoptosis: Bcl-2-related proteins gel connected. Curr. Biol. 7: R277-R281
72. Gajewski T. F. and Thompson C. B. (1996) Apoptosis meets signal transduction: elimination of a BAD influence. Cell 87: 589-592
73. L and Bcl-2. EMBO J. 16: 968-977
74. Halder S., Jena N. and Croce C. (1995) Inactivation of Bcl-2 by phosphorylation. Proc. Natl. Acad. Sci. USA 92: 4507-4511
75. Harrington E. A., Bennett M. R., Fanidi A. and Evan G. I. (1994) C-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J. 13: 3286-3295
76. Allsopp T. E., Wyatt S., Paterson H. F. and Davies A. M. (1993) The proto-oncogene bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis. Cell 73: 295-307
77. Kinoshita T., Yokota T., Arai K.-I. and Miyajima A. (1995) Suppression of apoptotic death in hematopoietic cells by signalling through the IL-3/GM-CSF receptors. EMBO J. 14: 266-275
78. Wang H.-G., Miyashita T., Takayama S., Sato T., Torigoe T., Krajewski S. et al. (1994) Apoptosis regulation by interaction of bcl-2 protein and Raf-1 kinase. Oncogene 9: 2751-2756
79. Wang H.-G., Rapp U. R. and Reed J. C. (1996) Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell 87: 629-638
80. Yao R. and Cooper G. M. (1995) Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science 267: 2003-2006
81. Datta S. R., Dudek H., Tao X., Masters S., Fu H., Gotoh Y. et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91: 231-241
82. L. Cell 87: 619-628
83. Xia Z., Dickens M., Raingeaud J., Davis R. J. and Greenberg M. E. (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270: 1326-1331
84. Chen Y.-R., Wang X., Templeton D., Davis R. J. and Tan T.-H. (1996) The role of c-Jun NH-terminal kinase (JNK) in apopotisis induced by ultraviolet C and γ radiation. J. Biol. Chem. 271: 31929-31936
85. Graves J. D., Draves K. E., Craxton A., Saklatvala J., Krebs E. G. and Clark E. A. (1996) Involvement of stress-activated protein kinase and p38 mitogen-activated protein kinase in mlaM-induced apoptosis of human B lymphocytes. Proc. Natl. Acad. Sci. USA 93: 13814-13818
86. Yang X., Khosravi-Far R., Chang H. Y. and Baltimore D. (1997) Daxx, a novel Fas-binding protein that activates JNK and apoptosis. Cell 89: 1067-1076
87. Verheij M., Bose R., Lin X. H., Yao B., Jarvis W. D., Grant S. et al. (1996) Requirement for ceramide-initiated SAPK/ JNK signalling in stress-induced apoptosis. Nature 380: 75-79
88. Mandrell K., Antonsson B., Magnenat E., Camps M., Muda M., Chabert C. et al. (1997) Bcl-2 undergoes phosphorylation by c-Jun N-terminal kinase/stress-activated protein kinase in the presence of the constitutively active GTP-binding protein Racl. J. Biol. Chem. 272: 25238-25242
89. L and Bcl-2. FMBO J. 16: 968-977
90. Horiuchi M., Hayashida W., Kambe T., Yamada T. and Dzau V. J. (1997) Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activaled protein kinase phosphatase-1 and induces apoptosis. J. Biol. Chem. 272: 19022-19026
91. Strack P. R., Frey M. W., Rizzo C. J., Cordova B., George H. J., Meade R. et al. (1996) Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2. Proc. Natl. Acad. Sci. USA 93: 9571-9576
92. Ellis H. M. and Horvitz H. R. (1986) Genetic control of programmed cell death in the nematode C. elegans. Cell 44: 817-829
93. Yuan J., Shaham S., Ledoux S., Ellis H. M. and Horvitz H. R. (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme. Cell 75: 641-652
94. Miura M., Zhu H., Rotello R., Hartwieg E. and Yuan J. (1993) Induction of apoptsis in fibroblasts by II-1B-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell 75: 653-660
95. Ray C. A., Black R. A., Kronheim S. R., Greenstrteet T. A., Sleath P. R., Salvesen G. S. et al. Viral inhibition of inflamation: cowpox virus encodes an inhibitor of the interleulin-1B-converting enzyme. Cell 69: 597-604
96. Fernandes-Alnemri T., Litwack G. and Alnemri E. S. (1994) CPP32, a novel human apoptotic protein with homology to C. elegans cell death ced-3 and mammalian interleukin-1B-converting enzyme. J. Biol. Chem. 269: 30761-30764
97. Nicholson D. W., Ali A., Thornberry N. A., Vaillancourt J. P., Ding C. K., Gallant M. et al. (1995) Identification and inhibition of the ice/ced-3 protease necessary for mammalian apoptosis. Nature 376: 37-43
98. Schlegel J., Peters I., Orrenius S., Miller D. K., Thornberry N. A., Yaamin T. et al. (1996) CPP32/apopain is a key interleukin-1B-converting enzyme-like protease involved in Fas-mediated apoptosis. J. Biol. Chem. 271: 1841-1844
99. Alnemri E. S., Livingston D. J., Nicholson D. W., Salvesen G., Thornberry N. A., Wong W. W. et al. (1996) Human ICE/CED-3 protease nomenclature. Cell 87: 171
100. Walker N. P. C, Talanian R. V., Brady K. D., Dang L. C., Bump N. J., Ferenz C. R. et al. (1994) Crystal structure of the cysteine protease interleukin-1B-converting enzyme: a (p20/ p10)2 homodimer. Cell 78: 343-352
101. Thornberry N. A., Bull H. G., Calaycay J. R., Chapman K. T., Howard A. D., Kostura M. J. et al. (1992) A novel heterodimeric cysteine protease is required for intrleukin-1B processing in monocytes. Nature 356: 768-774
102. Wilson K. P., Black A. F., Thomson J. A., Kim E. E., Griffith J. P., Navia M. A. et al. (1994) Structure and mechanism of interleukin-1B-converting enzyme. Nature 370: 270-275
103. Oppenheim R. W. (1991) Cell death during development of the nervous system. Ann. Rev. Neurosci. 14: 453-501
104. Clayton L. K., Ghendler Y., Mizoguchi E., Patch R. J., Ocaain T. D., Orth K. et al. (1997) T cell receptor ligation by peptide/MHC induces activation of a caspase in immature thymocytes: the molecular basis of negative selection. EMBO J. 16: 2282-2293
105. Zhong L. T., Sarafian T., Kane D. J., Charles A. C., Mah S. P., Edwards R. H. et al. (1993) Expression of bcl-2 inhibits neural death induced by multiple agents. Proc. Natl. Acad. Sci. USA 90: 4533-4537
106. Clem R. J., Fechheimer M. and Miller L. K. (1991) Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science 254: 1388-1390
107. Beidler D. R., Tewari M., Friesen P. D., Poiriers G. and Diixit V. M. (1995) The baculovirus p35 protein inhibits Fas and tumor necrosis factor induced apoptosis. J. Biol. Chem. 270: 16526-16528
108. Bump N. J., Hackett M., Hugunin M., Seshagiri S., Brady K., Chen P. et al. (1995) Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35. Science 269: 1885-1888
109. Manji G. A., Hozak R. R., LaCount D. J. and Friesen P. D. (1997) Baculovirus inhibitor of apoptosis functions at or upstream of the apoptotic suppressor p35 to prevent programmed cell death. J. Virol. 71: 4509-4516
110. Devereaux Q. L., Takahashi R., Salvesen G. S. and Reed J. C. (1997) X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388: 300-304
111. McKeon F. (1991) Nuclear lamin proteins: domains required for nuclear targeting, assembly and cell-cycle regulated dynamics. Curr. Opin. Cell. Biol. 3: 82-86
112. Oberhammer F. A., Hochegger K., Froschl G. and Tiefenbacher R. (1994) Chromatin condensation during apoptosis is accompanied by degradation of lamin A and B without enhanced activation of cdc2 kinase. J. Cell Biol. 126: 827-8377
113. Draetta G. Cell cycle control in eukaryotes: molecular mechanisms of cdc2 activation. Trends Biochem. Sci. 15: 378-383
114. Peter M., Nakagawa J., Doree M., Labbe J. C. and Nigg E. A. (1990) In vitro disassembly of the nuclear lamina and M-phase specific phosphorylation of lamins by cdc2 kinase. Cell 61: 591-602
115. Lazebnik Y. A., Cole S., Cooke C. A., Nelson W. G. and Earnshaw W. C. (1993) Nuclear events of apoptosis in vitro in cell free mitotic extracts: a model system for analysis of the active phase of apoptosis. J. Cell Biol. 123: 7-22
116. Lazebnik Y. A., Takahashi A., Moir R., Goldman R., Poirier G., Kaufmann S. et al. (1995) Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution. Proc. Natl. Acad. Sci. USA 92: 9042-9046
117. Rao L., Perez D. and White E. (1996) Lamin proteolysis facilitates nuclear events during apoptosis. J. Cell Biol. 135: 1441-1455
118. Satoh M. S. and Lindahl T. (1992) Role of poly(ADP-ribose) formation in DNA repair. Nature 356: 356-358
119. Ding R., Pommier Y., Kang V. H. and Smulson M. (1992) Depletion of poly(ADP-ribose) polymerase by antisense RNA expression results in delay in DNA strand break rejoining. J. Biol. Chem. 267: 12804-12812
120. Lazebnik Y. A., Kaufmann S. H., Desnoyers S., Poirier G. G. and Earnshaw W. C. (1994) Cleavage of poly (ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371: 346-347
121. Wyllie A. H. (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284: 555-556
122. Tanaka Y., Yoshihara K., Itaya A., Kamiya T. and Koide S. S. (1984) Mechanism of the inhibition of Ca+2, Mg+2 dependent endonuclease of bull seminal plasma induced by ADP-ribosylation. J. Biol. Chem. 259: 6579-6585
123. Ubeda M. and Habener J. F. (1997) The large subunit of the DNA replication complex C (DSEB/RF-C140) cleaved and inactivated by caspase3 (CPP32/YAMA) during Fas-induced apoptosis. J. Biol. Chem. 272: 19562-19568
124. Liu X., Zou H., Slaughter C. and Wang X. (1997) DFF, a heterodimeric protein that functions downstream of caspase3 to trigger DNA fragmentation during apoptosis. Cell 89: 1775-184
125. Rudel T. and Bokoch G. (1997) Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2. Science 276: 1571-1574
126. Brzeska H., Knaus U. G., Wang Z., Bokoch G. M. and Korn E. D. (1997) p21 activated kinase has substrate specificity similar to the Acanthamoeba myosin 1 heavy chain kinase and activates Acanthamoeba myosin 1. Proc. Natl. Acad. Sci. USA 94: 1092-1095
127. Challappan S. P., Hiebert S., Mudryj M., Horowitz J. M. and Nevins J. R. (1991) The E2F transcription factor is a cellular target for the RB protein. Cell 65: 1053-1061
128. Shirodkar S., Ewen M., DeCaprio J. A., Morgan J., Livingston D. M. and Chittenden T. (1992) The transcription factor E2F interacts with the retinoblastoma product and a p107-cyclin A complex in a cell cycle-regulated manner. Cell 68: 157-166
129. Bagchi S., Weinmann R. and Raychaudhuri P. (1991) The retinoblastoma protein copurifies with E2F-1, an E1A-regulated inhibitor of the transcription factor E2F. Cell 65: 1063-1072
130. Meikrantz W., Gisselbrecht S., Tam S. W. and Schlegel R. (1994) Activation of cyclin A-dependent protein kinases during apoptosis. Proc. Natl. Acad. Sci. USA 91: 3754-3758
131. Shan B., Farmer A. A. and Lee W. H. (1996) The molecular basis of E2F-1/DP-1-induced S-phase entry and apoptosis. Cell Growth Diff. 7(6): 689-697
132. Clarke A., Maandag E., Van Toon M., Van der Lugt N., Van der Valk M., Hooper M. et al. (1992) Requirement for a functional Rb-1 gene in murine development. Nature 359: 328-330
133. Fuchs E. J., McKenna K. A. and Bedi A. (1997) p53-dependent DNA damage-induced apoptosis requires Fas/APO-1-independent activation of CPP32 beta. Cancer Res. 57: 2550-2554
134. Dou Q. P., An B., Antoku K. and Johnson D. F. (1997) Fas stimulation induces RB dephosphorylation and proteolysis that is blocked by inhibitors of the ICE protease family. J. Cell Biochem. 64(4): 586-594
135. Tan X., Martin S. J., Green D. R. and Wang J. Y. J. (1997) Degradation of retinoblastoma protein in tumor necrosis factor-and CD95-induced cell death. J. Biol. Chem. 272: 9613-9616
136. Janicke R. U., Walker P. A., Lin X. Y. and Porter A. G. (1996) Specific cleavage of the retinoblastoma protein by an ICE-like protease in apoptosis. EMBO J. 15(24): 6969-6978
137. Chen W. D., Otterson G. A., Lipkowitz S., Khleif S. N., Coxon A. B. and Kaye F. J. (1997) Apoptosis is associated with cleavage of a 5 kDa fragment from RB which mimics dephosphorylation and modulates E2F binding. Oncogene 14: 1243-1248
138. An B. and Dou Q. P. (1996) Cleavage of retinoblastoma protein during apoptosis: an interleukin 1 beta-converting enzyme-like protease as candidate. Cancer Res. 56: 438-442
139. An B., Jin J. R., Lin P. and Dou Q. P. (1996) Failure to activate interleukin 1beta converting enzyme-like proteases and to cleave retinoblastoma protein in drug-resistant cells. FEBS Lett. 399: 158-162
140. Brakebusch C., Nophar Y., Kemper O., Englemann H. and Wallach D. (1992) Cytoplasmic truncation of the p55 tumor necrosis factor (TNF) receptor abolishes signalling, but not induced shedding of the receptor. EMBO J. 11: 943-950
141. Tartaglia L. A., Ayres T. M., Wong G. H. and Goeddel D. V. (1993) A novel domain within the 55kd TNF receptor signals cell death. Cell 74: 845-853
142. Itoh N. and Nagata S. (1993) A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen. J. Biol. Chem. 268: 10932-10937
143. Fraser A. and Evan G. (1996) A license to kill. Cell 85: 781-784
144. Kischkel F. C., Hellbardt S., Behrmann I., Germer M., Pawlita M., Krammer P. H. et al. (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signalling complex (DISC) with the receptor. EMBO J. 14:5579-5588
145. Masato E., Hug H. and Nagata S. (1995) Involvement of an ICE-like prottease in Fas-mediated apoptosis. Nature 375: 78-81
146. Los M., Van de Craen M., Penning L., Schenk H., Westendorp M., Bueuerle P. et al. (1995) Requirement of an ICE/ CED3 protease for Fas/APO-1 mediated apoptosis. Nature 375: 81-83
147. Takahashi A., Hirata H., Yonehara S., Imai Y., Lee K. K., Moyer R. W. et al. (1997) Affinity labeling displays the stepwise activation of ICF related proteases by Fas, staurosporine, and Crm-A sensitive caspase8. Oncogene 14: 2741-2752
148. Irmler M., Thome M., Hahne M., Schneider P., Hofmann K., Steiner V. et al. (1997) Inhibition of death receptor signals by cellular FLIP. Nature 388: 190-195
149. Boldin M. P., Gonccharov T. M., Goltsev Y. V. and Wallach D. (1996) Involvement of MACH, a novel MORT1/FADD interacting protease, in Fas/APO-1 and TNF receptor-induced cell death. Cell 85: 803-8155
150. Harvey N. L., Butt A. J. and Kumar S. (1997) Functional activation of Nedd2/ICH-1 (caspase2) is an early process in apoptosis. J. Biol. Chem. 272: 13134-13139
151. Chinnaiyan A. M., O'Rourke K., Lane B. R. and Dixit V. M. (1997) Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death. Science 275: 1122-1126
152. Faleiro L., Kobayashi R., Fearnhead H. and Lazebnik Y. (1997) Multiple species of CPP32 and Mch2 are the major active caspases present in apoptotic cells. EMBO J. 16: 2271-2281
153. Martins L. M., Kottke T., Messner P. W., Basi G. S., Sinha S., Frigon N. Jr et al. (1997) Activation of multiple interleukin-1beta converting enzyme homologues in cytosol and nuclei of HL-60 cells during etoposide-induced apoptosis. J. Biol. Chem. 272: 7421-7430
154. Boldin M. P., Varfolomeev E. E., Pancer Z., Mett I. L., Camonis J. H. and Wallach D. (1995) A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain. J. Biol. Chem. 270: 7795-7798
155. Chinnaiyan A. M., O'Rourke K., Tewari M. and Dixit V. M. (1995) FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81: 505-512
156. Chinnaiyan A. M., Tepper C. G., Seldinn M. F., O'Rourke K, Kischkel F. C., Hellbardt S. et al. (1996) FADD/MORT1 is a common mediatorr of CD95(Fas/APO1) and tumor necrosis factor receptor-induced apoptosis. J. Biol. Chem. 271: 4961-4965
157. Hsu H., Xiong J. and Goeddel D. V. (1995) The TNF receptor-1 associated protein TRADD signals cell death and NF-κB activation. Cell 81: 495-504
158. Boldin M. P., Goncharov T. M., Goltsev Y. V. and Wallach, D. (1996) Involvement of MACH, a novel MORT1/FADD interacting protease, in Fas/APO1 and TNF receptor induced cell death. Cell 85: 803-815
159. Hsu H., Shu H.-B., Pan M.-P. and Goeddel D. V. (1996) TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor-1 signal transduction pathways. Cell 84: 299-308
160. Muzio M., Chinnaiyan A. M., Kischkel F. C., O'Rourke K., Shevchenko A., Ni J. et al. (199) FLICE, a novel FADD-homologous ICE/Ced3-like protease is recruited to the CD95 (Fas/APO-1) death-inducing signalling complex. Cell 85: 817-827
161. Hu S., Vincenz C., Ni J., Gentz R. and Dixit V. M. (1997) I-FLICE, a novel inhibitor of tumor necrosis factor rcceptor-1 and CD-95 induced apoptosis. J. Biol. Chem. 272: 17255-17257
162. Stanger B. Z., Leder P., Lee T.-H., Kim E. and 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
163. Hsu H, Huang J., Shu H.-B., Baaichwal V. and Goeddel D. V. (1996) TNF dependent recruitment of the protein kinase RIP to the TNF receptor-1 signalling complex. Immunity 4: 387-396
164. Fischen C. M., Dick C. J. and Leibson P. J. Tyrosine kinase activation provides an early and requisite signal for Fas-induced apoptosis. J. Immunol. 153: 1947-1954
165. Ahmad M., Srinivasula S. M., Wang L., Talanian R. V., Litwack G., Fernandes-Alnemri T. et al. (1997) CRADD, a novel human apoptotic adaptor molecule for caspase 2 and Fas/tumor necrosis factor receptor-interacting protein RIP. Cancer Res. 57: 615-619
166. Duan H. and Dixit V. M. (1997) RAIDD is a new death adaptor molecule. Nature 385: 86-89
167. Kamada S., Washida M., Hasegawa J., Kusano H., Funahashi Y. and Tsujimoto Y. (1997) Involvement of caspase 4-like protease in Fas mediated apoptotic pathway. Oncogene 15: 285-290
168. Beg A. A. and Baltimore D. (199) An essential role for NF-κB in preventing TNF-α-induced cell death. Science 274: 782-784
169. Wang C.-Y., Mayo M. W. and Baldwin A. S. Jr (1996) TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-κB. Science 274: 784-787
170. Van Antwerp D. J., Martin S. J., Kafri T., Green D. R. and Verma I. M. (1996) Suppression of TNF-α-induced apoptosis by NF-κB. Science 274: 787-789
171. Rothe M., Wong S. C., Henzel W. J. and Goeddel D. V. (1994) A novel family of putative signal transducers associated with the cytoplasmic domain of the 75kDa tumor necrosis factor receptor. Cell 78: 681-692
172. Liu Z.-G., Hsu H., Goeddel D. V. and Karin M. (1996) Dissection of the TNF receptor-1 effector functions: JNK activation is not linked to apoptosis while NF-κB activation prevents cell death. Cell 87: 565-576
173. Darnell J. E. Jr, Kerr I. M. and Stark G. R. (1994) Jak-stat pathways and transcriptional activation in response to INFs and other extracellular signalling proteins. Science 264: 1415-1421
174. Jung Y., Miura M. and Yuan J. (199) Suppression of interleukin-1 beta converting enzyme mediated cell death by insulin-like growth factor. J. Biol. Chem. 271: 5112-5117
175. Van der Geer P., Hunter T. and Lindberg R. (1994) Receptor protein tyrosine kinases and their signal transduction pathways. Annu. Rev. Cell. Biol. 10: 251-337
176. Ben-Bassat H., Rosenbaum-Mitrani S., Hartzstark Z., Shlomai Z., Kleinberger-Doron N., Gaazit A. et al. (1997) Inhibitors of epidermal growth factor receptor kinase and of cyclin-dependent kinase 2 activation induce growth arrest, differentiation and apoptosis of human papilloma virus 16-immortalized human keratinocytes. Cancer Res. 57: 3741-3750
177. Kimchi A. (1992) Cytokine triggered molecular pathways that control cell cycle arrest. J. Cell. Biochem. 50: 1-9
178. Chin Y. E., Kitagawa M., Su W.-C. S., You Z.-H., Iwamoto Y. and Fu X.-Y. (1996) Cell growth arrest and induction of cyclin dependent kinase inhibitor p21 waf/cip1 mediated by STAT1. Science 272: 719-722
179. Chin Y. E., Kitagawa M., Kuida K., Flavell R. and Fu X.-Y. (1997) Activation of the STAT signalling pathway can cause expression of caspasel and apoptosis. Mol. Cell. Biol. 17: 5328-5337
180. Dolle R. E., Hoyer D., Prasad C. V., Schmidt S. J., Helaszek C. T., Miller R. E. et al. (1994) P1 aspartate based peptide alpha-((2, 6-dichlorobenzoyl)oxy)methyl ketones as potent time dependent inhibitors of interleukin-1 beta converting enzyme. J. Med. Chem. 37: 563-564
181. Angel P. and Karin M. (1991) The role of jun, fos, and the AP-1 complex in cell proliferation and transformation. Biochim. Biophys. Acta. 1072: 129-157
182. Bossy-Wetzel E., Bakiri L. and Yaniv M. (1997) Induction of apoptosis by the transcription factor c-jun. EMBO J. 16: 1695-1709
183. Atfi A., Buisine M., Mazars A. and Gespach C. (1997) Induction of apoptosis by DPC4, a transcriptional factor regulated by transforming growth factor-B through stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) signalling pathway. J. Biol. Chem. 272: 24731-24734
184. Boulakia C. A., Chen G., Ng F. W. H., Teodoro J. G., Branton P. E., Nicholson D. W. et al. (1996) Bcl-2 and adenovirus E1B 19kDA protein prevent E1A-induced processing of CPP32 and cleavage of poly(ADP-ribose) polymerase. Oncogene 12: 529-535
185. Shimizu S., Eguchi Y., Kamiike W., Matsuda H. and Tsujimoto Y. (1996) Bcl-2 expression prevents activation of the ICE protease cascade. Oncogene 12: 2251-2257
186. Spector M. S., Desnoyers S., Hoeppner D. J. and Hengartner M. O. (1997) Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature 385: 653-656
187. Wu D., Wallen H. D. and Nunez G. (1997) Interaction and regulation of subcellular localization of CED-4 by CED-9. Science 275: 1126-1128
188. Shaham S. and Horvitz H. R. (1996) Developing Caenorhabditis elegans neurons may contain both cell-death protective and killer activities. Genes Dev. 10: 578-591
189. Wu D., Wallen H. D., Inohara N. and Nunez G. (1997) Interaction and regulation of the Caenorhabditis elegans death protease CED-3 by CED-4 and CED-9. J. Biol. Chem. 272: 21449-21454
190. James C., Gschmeissner S., Fraser A. and Evan G. I. (1997) CED-4 induces chromatin condensation in Schizosaccharomyces pombe and is inhibited by direct physical association with CED-9. Curr. Biol. 7: 246-252
191. Seshagiri S. and Miller L. (1997) Caenorhabditis elegans CED-4 stimulates CED-3 processing and CED-3-induced apoptosis. Curr. Biol. 7: 455-460
192. Chinnaiyan A. M., Chaudhary D., O'Rourke K., Koonin E. V. and Dixit V. M. (1997) Role of CED-4 in the activation of CED-3. Nature 388: 728-729
193. Chinnaiyan A. M., O'Rourke K., Lane B. R. and Dixit V. M. (1997) Interaction of CED-4 with CED-3 and CED-9: A molecular framework for cell death. Science 275: 1122-1126
194. Liu X., Kim C. N., Yang J., Jemmerson R. and Wang X. (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86: 147-157
195. Zou H., Henzel W. J., Liu X., Lutschg A. and Wang X. (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90: 405-413
196. Hoffman K., Bucher P. and Tschopp J. (1997) The CARD domain: a new apoptotic signalling motif. Trends Biochem. Sci. 22: 155-156
197. Li P., Nijhawan D., Budihardjo L, Srinivasula S. M., Ahmad M., Alnemri E. S. et al. (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91: 479-489
198. Chinnaiyan A. M., Orth K., O'Rourke K., Duan H., Poirier G. G. and Dixit V. M. (1997) Molecular ordering of the cell death pathway. Bcl-2 and Bcl-xL function upstream of the CED-3-like apoptotic proteases. J. Biol. Chem. 271: 4573-4576
199. Erhardt P. and Cooper G. M. (1996) Activation of the CPP32 apoptotic protease by distinct signalling pathways with differential sensitivity to Bcl-xL. J. Biol. Chem. 271: 17601-17604
200. Cohen G. M. (1997) Caspases: the executioners of apoptosis. Biochem. J. 326: 1-16