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Apoptosis

Molecules and Mechanisms

  • Chapter
Drug Resistance in Leukemia and Lymphoma III

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 457))

Abstract

This review of the molecules and pathways involved in programmed cell death (apoptosis) discriminates triggers of apoptosis (e.g. chemotherapy, radiation, Fas ligation), modulators of apoptosis (e.g. Bcl-2 family members, Bcl-2 interacting proteins, Apafs, IAPs, and Fas/FasL modulators including FLICE and FLIPs), effectors (caspases 1–13) and cleavage substrates (e.g. PARP). Special consideration is given to the structure-function relationship of Bcl-2 family members and to their post-transcriptional modification. Brief references are made to the role of apoptotic pathway in leukemias and lymphomas and to strategies of modulating apoptotic pathways.

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References

  1. White E. Life, death, and the pursuit of apoptosis. Genes Dev 1996;10(1):1–15

    PubMed  CAS  Google Scholar 

  2. Yang E, Korsmeyer SJ. Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood 1996;88(2):386–401

    PubMed  CAS  Google Scholar 

  3. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995;267(5203):1456–1462

    PubMed  CAS  Google Scholar 

  4. Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J. Human ICE/CED-3 protease nomenclature. Cell 1996;87(2):171

    PubMed  CAS  Google Scholar 

  5. Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 1993;75(4):641–652

    PubMed  CAS  Google Scholar 

  6. Hengartner MO, Horvitz HR. Programmed cell death in Caenorhabditis elegans. [Review] [45 refs] Curr Opin Genet Dev 1994;4(4):581–586

    CAS  Google Scholar 

  7. Vaux DL, Weissman IL, Kim SK. Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2. Science 1992;258(5090):1955–1957

    PubMed  CAS  Google Scholar 

  8. Nicholson DW, Thornberry NA. Caspases: killer proteases. Trends Biochem Sci 1997;22(8):299–306

    PubMed  CAS  Google Scholar 

  9. Talanian RV, Quinlan C, Trautz S, Hackett MC, Mankovich JA, Banach D, Ghayur T, Brady KD, Wong WW. Substrate specificities of caspase family proteases. J Biol Chem 1997;272(15):9677–9682

    PubMed  CAS  Google Scholar 

  10. Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA, Roy S, Vaillancourt JP, Chapman KT, Nicholson DW. A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem 1997;272(29):17907–17911

    PubMed  CAS  Google Scholar 

  11. Fernandes-Alnemri T, Armstrong RC, Krebs J, Srinivasula SM, Wang L, Bullrich F, Fritz LC, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES. In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. Proc Natl Acad Sci U S A 1996;93(15):7464–7469

    PubMed  CAS  Google Scholar 

  12. Boldin MP, Goncharov TM, Goltsev YV, Wallach D. Involvement of MACH, a novel MORTI/FADD-interacting protease, in Fas/APO-1-and TNF receptor-induced cell death. Cell 1996;85(6):803–815

    PubMed  CAS  Google Scholar 

  13. Muzio M, Chinnaiyan AM, Kischkel FC, O’Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death—inducing signaling complex. Cell 1996;85(6):817–827

    PubMed  CAS  Google Scholar 

  14. Faleiro L, Kobayashi R, Fearnhead H, Lazebnik Y. Multiple species of CPP32 and Mch2 are the major active caspases present in apoptotic cells. EMBO J 1997;16(9):2271–2281

    PubMed  CAS  Google Scholar 

  15. Martins LM, Kottke T, Mesner PW, Basi GS, Sinha S, Frigon N Jr, Tatar E, Tung JS, Bryant K, Takahashi A, Svingen PA, Madden BJ, McCormick DJ, Earnshaw WC, Kaufmann SH. Activation of multiple interleukin-1 beta converting enzyme homologues in cytosol and nuclei of HL-60 cells during etoposide-induced apoptosis. J Biol Chem 1997;272(11):7421–7430

    PubMed  CAS  Google Scholar 

  16. MacFarlane M, Cain K, Sun XM, Alnemri ES, Cohen GM. Processing/activation of at least four interleukin-1beta converting enzyme-like proteases occurs during the execution phase of apoptosis in human monocytic tumor cells. J Cell Biol 1997;37(2):469–479

    Google Scholar 

  17. Takahashi A, Hirata H, Yonehara S, Imai Y, Lee KK, Moyer RW, Turner PC, Mesner PW, Okazaki T, Sawai H, Kishi S, Yamamoto K, Okuma M, Sasada M. Affinity labeling displays the stepwise activation of ICE-related proteases by Fas, staurosporine, and CrmA-sensitive caspase-8. Oncogene 1997;14(23):2741–2752

    PubMed  CAS  Google Scholar 

  18. Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, Robertson N, Armstrong RC, Wang L, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES. 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 1996;271(43):27099–27106

    PubMed  CAS  Google Scholar 

  19. Fernandes-Alnemri T, Takahashi A, Armstrong R, Krebs J, Fritz L, Tomaselli KJ, Wang L, Yu Z, Croce CM, Salveson G, et al. Mch3, a novel human apoptotic cysteine protease highly related to CPP32. Cancer Res 1995;55(24):6045–6052

    PubMed  CAS  Google Scholar 

  20. Humke EW, Ni J, Dixit VM. ERICE, a novel FLICE-activatable caspase. Biol Chem 1998;273(25):15702–15707

    CAS  Google Scholar 

  21. Estrov Z, Thall PF, Talpaz M, Estey EH, Kantarjian H, Andreeff M, Harris D, Van Q, Walterscheid M, Kornblau S. Caspase 2 and caspase 3 protein levels as predictors of survival in acute myelogenous leukemia. Blood 1998;92(9):3090–3097

    PubMed  CAS  Google Scholar 

  22. Lisovsky M, Estrov Z, Zhang X, Consoli U, Sanchez-Williams G, Snell V, Munker R, Goodacre A, Savchenko V, Andreeff M. Flt3 ligand stimulates proliferation and inhibits apoptosis of acute myeloid leukemia cells: regulation of Bcl-2 and Bax. Blood 1996;88(10):3987–3997

    PubMed  CAS  Google Scholar 

  23. Consoli U, El-Tounsi I, Sandoval A, Snell V, Kleine HD, Brown W, Robinson JR, DiRaimondo F, Plunkett W, Andreeff M. Differential induction of apoptosis by fludarabine monophosphate in leukemic B and normal T cells in chronic lymphocytic leukemia. Blood 1998;91(5):1742–1748

    PubMed  CAS  Google Scholar 

  24. Nagata S. Apoptosis by death factor. Cell 1997;88(3):355–365

    PubMed  CAS  Google Scholar 

  25. Nagata S, Golstein P. The Fas death factor. Science 1995;267(5203):1449–1456

    PubMed  CAS  Google Scholar 

  26. Munker R, Marini F, Jiang S, Savary C, Owen-Schaub L, Andreeff M. Expression of CD95(FAS) by gene transfer does not sensitize K562 to Fas-killing. Hematol Cell Ther 1997;39(2):75–78

    PubMed  CAS  Google Scholar 

  27. Munker R, Andreeff M. Induction of death (CD95/FAS), activation and adhesion (CD54) molecules on blast cells of acute myelogenous leukemias by TNF-alpha and IFN-gamma. Cytokines Mol Ther 1996;2(3):147–159

    PubMed  CAS  Google Scholar 

  28. Hitoshi Y, Lorens J, Kitada SI, Fisher J, LaBarge M, Ring HZ, Francke U, Reed JC, Kinoshita S, Nolan GP. Toso, a cell surface, specific regulator of Fas-induced apoptosis in T cells. Immunity 1998;8(4):461–471

    PubMed  CAS  Google Scholar 

  29. Younes A, Snell V, Consoli U, Clodi K, Zhao S, Palmer JL, Thomas EK, Armitage RJ, Andreeff M. Elevated levels of biologically active soluble CD40 ligand in the serum of patients with chronic lymphocytic leukaemia. Br J Haematol 1998;100(1):135–141

    PubMed  CAS  Google Scholar 

  30. Clodi K, Asgari Z, Macduff BM, Zhao S, Kliche K-O, Palmer JL, Cabanillas F, Andreeff M, Younes A. A potential autocrine loop involving CD40 ligand in B cell lymphoma. Submitted

    Google Scholar 

  31. Younes A, Consoli U, Snell V, Clodi K, Kliche KO, Palmer JL, Gruss HJ, Armitage R, Thomas EK, Cabanillas F, Andreeff M. CD30 ligand in lymphoma patients with CD30+ tumors. J Clin Oncol 1997;15(11):3355–3362

    PubMed  CAS  Google Scholar 

  32. Marsters SA, Sheridan JP, Pitti RM, Brush J, Goddard A, Ashkenazi A. Identification of a ligand for the death-domain-containing receptor apo3. Curr Biol 1998;8(9):525–528

    PubMed  CAS  Google Scholar 

  33. Boldin MP, Varfolomeev EE, Pancer Z, Mett IL, Camonis JH, Wallach D. A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain. J Biol Chem 1995;270(14):7795–7798

    PubMed  CAS  Google Scholar 

  34. Chinnaiyan AM, O’Rourke K, Tewari M, Dixit VM. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 1995;81(4):505–512

    PubMed  CAS  Google Scholar 

  35. Chinnaiyan AM, Tepper CG, Seldin MF, O’Rourke K, Kischkel FC, Hellbardt S, Krammer PH, Peter ME, Dixit VM. FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. J Biol Chem 1996;271(9):4961–4965

    PubMed  CAS  Google Scholar 

  36. Duan H, Dixit VM. RAIDD is a new ‘death’ adaptor molecule. Nature 1997 Jan 2;385(6611):86–89

    PubMed  CAS  Google Scholar 

  37. Boldin MP, Goncharov TM, Goltsev YV, Wallach D. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1-and TNF receptor-induced cell death. Cell 1996;85(6):803–815

    PubMed  CAS  Google Scholar 

  38. Muzio M, Chinnaiyan AM, Kischkel FC, O’Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death—inducing signaling complex. Cell 1996;85(6):817–827

    PubMed  CAS  Google Scholar 

  39. Inohara N, del Peso L, Koseki T, Chen S, Nunez G. RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. J Biol Chem 1998;273(20):12296–12300

    PubMed  CAS  Google Scholar 

  40. Strand S, Hofmann WJ, Hug H, Muller M, Otto G, Strand D, Mariani SM, Stremmel W, Krammer PH, Galle PR. Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells—a mechanism of immune evasion?. Nat Med 1996;2(12):1361–1366

    PubMed  CAS  Google Scholar 

  41. Hahne M, Rimoldi D, Schroter M, Romero P, Schreier M, French LE, Schneider P, Bornand T, Fontana A, Lienard D, Cerottini J, Tschopp J. Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science 1996;274(5291):1363–1366

    PubMed  CAS  Google Scholar 

  42. O’Connell J, O’Sullivan GC, Collins JK, Shanahan F. The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med 1996;184(3):1075–1082

    PubMed  Google Scholar 

  43. Munker R, Midis G, Owen-Schaub L, Andreff M. Soluble FAS (CD95) is not elevated in the serum of patients with myeloid leukemias, myeloproliferative and myelodysplastic syndromes. Leukemia 1996;10(9):1531–1533

    PubMed  CAS  Google Scholar 

  44. Friesen C, Herr I, Krammer PH, Debatin KM. Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nat Med 1996;2(5):574–577

    PubMed  CAS  Google Scholar 

  45. Herr I, Wilhelm D, Bohler T, Angel P, Debatin KM. Activation of CD95 (APO-1/Fas) signaling by ceramide mediates cancer therapy-induced apoptosis. EMBO J 1997;16(20):6200–6208

    PubMed  CAS  Google Scholar 

  46. Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer JL, Schroter M, Scaffidi C, Krammer PH, Peter ME, Tschopp J. Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 1997;386(6624):517–521

    PubMed  CAS  Google Scholar 

  47. Senkevich TG, Bugert JJ, Sisler JR, Koonin EV, Darai G, Moss B. Genome sequence of a human tumorigenic poxvirus: prediction of specific host response-evasion genes. Science 1996;273(5276):813–816

    PubMed  CAS  Google Scholar 

  48. Bodmer JL, Burns K, Schneider P, Hofmann K, Steiner V, Thome M, Bornand T, Hahne M, Schroter M, Becker K, Wilson A, French LE, Browning JL, MacDonald HR, Tschopp J. TRAMP, a novel apoptosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas(Apo-1/CD95). Immunity 1997;6(1):79–88

    PubMed  CAS  Google Scholar 

  49. Kitson J, Raven T, Jiang YP, Goeddel DV, Giles KM, Pun KT, Grinham CJ, Brown R, Farrow SN. A death-domain-containing receptor that mediates apoptosis. Nature 1996;384(6607):372–375

    PubMed  CAS  Google Scholar 

  50. Chinnaiyan AM, O’Rourke K, Yu GL, Lyons RH, Garg M, Duan DR, Xing L, Gentz R, Ni J, Dixit VM. Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95. Science 1996;274(5289):990–992

    PubMed  CAS  Google Scholar 

  51. Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J. Inhibition of death receptor signals by cellular FLIP. Nature 1997;388(6638):190–195

    PubMed  CAS  Google Scholar 

  52. Golstein P. Cell death: TRAIL and its receptors. Current Biol 1997;7:R750–R753

    CAS  Google Scholar 

  53. Snell V, Clodi K, Zhao S, Goodwin R, Thomas EK, Morris SW, Kadin ME, Cabanillas F, Andreeff M, Younes A. Activity of TNF-related apoptosis-inducing ligand (TRAIL) in haematological malignancies. Br J Haematol 1997;99(3):618–624

    PubMed  CAS  Google Scholar 

  54. Sato T, Irie S, Krajewski S, Reed JC. Cloning and sequencing of a cDNA encoding the rat Bcl-2 protein. Gene 1994;140(2):291–292

    PubMed  CAS  Google Scholar 

  55. Sedlak TW, Oltvai ZN, Yang E, Wang K, Boise LH, Thompson CB, Korsmeyer SJ. Multiple Bcl-2 family members demonstrate selective dimerizations with Bax. Proc Natl Acad Sci USA 1995;92(17):7834–7838

    PubMed  CAS  Google Scholar 

  56. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993;74(4):609–619

    PubMed  CAS  Google Scholar 

  57. Yang E, Zha J, Jockei J, Boise LH, Thompson CB, Korsmeyer SJ. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell 1995;80(2):285–291

    PubMed  CAS  Google Scholar 

  58. Otter I, Conus S, Ravn U, Rager M, Olivier R, Monney L, Fabbro D, Borner C. The binding properties and biological activities of bcl-2 and bax in cells exposed to apoptotic stimuli. J Biol Chem 1998;273(11):6110–6120

    PubMed  CAS  Google Scholar 

  59. Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 1993;74(4):597–608

    PubMed  CAS  Google Scholar 

  60. Motoyama N, Wang F, Roth KA, Sawa H, Nakayama K, Nakayama K, Negishi I, Senju S, Zhang Q, Fujii S, et al. Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science 1995;267(5203) 1506–1510

    PubMed  CAS  Google Scholar 

  61. Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW. MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proc Natl Acad Sci USA 1993;90(8):3516–3520

    PubMed  CAS  Google Scholar 

  62. Zhou P, Qian L, Kozopas KM, Craig RW. Mcl-1, a Bcl-2 family member, delays the death of hematopoietic cells under a variety of apoptosis-inducing conditions. Blood 1997;89(2):630–643

    PubMed  CAS  Google Scholar 

  63. Kaufmann SH, Karp JE, Svingen PA, Krajewski S, Burke PJ, Gore SD, Reed JC. Elevated expression of the apoptotic regulator Mcl-1 at the time of leukemic relapse. Blood 1998;91(3):991–1000

    PubMed  CAS  Google Scholar 

  64. Kitada S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S, Wang HG, Zhang X, Bullrich F, Croce CM, Rai K, Hines J, Reed JC. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with In vitro and In vivo chemoresponses. Blood 1998;91(9):3379–3389

    PubMed  CAS  Google Scholar 

  65. Lin EY, Orlofsky A, Berger MS, Prystowsky MB. Characterization of Al, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2. J Immunol 1993;151(4):1979–1988

    PubMed  CAS  Google Scholar 

  66. Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S. bcl-w, a novel member of the bcl-2 family, promotes cell survival. Oncogene 1996;13(4):665–675

    PubMed  CAS  Google Scholar 

  67. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993;74(4):609–619

    PubMed  CAS  Google Scholar 

  68. Zhou M, Demo SD, McClure TN, Crea R, Bitler CM. A novel splice variant of the cell death-promoting protein BAX. J Biol Chem 1998;273(19):11930–11936

    PubMed  CAS  Google Scholar 

  69. Meijerink JPP, Mensink EJBM, Wang K, Sedlak TW, Sloetjes AW, de Witte T, Waksman G, Korsmeyer SJ. Hematopoietic malignancies demonstrate loss-of-function mutations of bax. Blood 1998;91(8):2991–2997

    PubMed  CAS  Google Scholar 

  70. Yin XM, Oltvai ZN, Korsmeyer SJ. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature 1994;369(6478):321–323

    PubMed  CAS  Google Scholar 

  71. Chittenden T, Flemington C, Houghton AB, Ebb RG, Gallo GJ, Elangovan B, Chinnadurai G, Lutz RJ. A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. EMBO J 1995;14(22):5589–5596

    PubMed  CAS  Google Scholar 

  72. Zha H, Aime-Sempe C, Sato T, Reed JC. Proapoptotic protein Bax heterodimerizes with Bcl-2 and homodimerizes with Bax via a novel domain (BH3) distinct from BH1 and BH2. J Biol Chem 1996;271(13):7440–7444

    PubMed  CAS  Google Scholar 

  73. Hanada M, Aime-Sempe C, Sato T, Reed JC. Structure-function analysis of Bcl-2 protein. Identification of conserved domains important for homodimerization with Bcl-2 and heterodimerization with Bax. J Biol Chem 1995;270(20):11962–11969

    PubMed  CAS  Google Scholar 

  74. Cheng EH, Levine B, Boise LH, Thompson CB, Hardwick JM. Bax-independent inhibition of apoptosis by Bcl-XL. Nature 1996;379(6565):554–556

    PubMed  CAS  Google Scholar 

  75. Hunter JJ, Bond BL, Parslow TG. Functional dissection of the human Bc12 protein: sequence requirements for inhibition of apoptosis. Mol Cell Biol 1996;16(3):877–883

    PubMed  CAS  Google Scholar 

  76. Boyd JM, Gallo GJ, Elangovan B, Houghton AB, Malstrom S, Avery BJ, Ebb RG, Subramanian T, Chittenden T, Lutz RJ, et al. Bik, 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 1995;11(9):1921–1928

    PubMed  CAS  Google Scholar 

  77. O’Connor L, Strasser A, O’Reilly LA, Hausmann G, Adams JM, Cory S, Huang OC. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J 1998;17(2):384–395

    PubMed  Google Scholar 

  78. Muchmore SW, Sattler M, Liang H, Meadows RP, Harlan JE, Yoon HS, Nettesheim D, Chang BS, Thompson CB, Wong SL, Ng SL, Fesik SW. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 1996;381(6580):335–341

    PubMed  CAS  Google Scholar 

  79. Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS, Minn AJ, Thompson CB, Fesik SW. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 1997;275(5302):983–986

    PubMed  CAS  Google Scholar 

  80. Diaz JL, Oltersdorf T, Horne W, McConnell M, Wilson G, Weeks S, Garcia T, Fritz LC. A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members. J Biol Chem 1997;272(17):11350–11355

    PubMed  CAS  Google Scholar 

  81. Kiefer MC, Brauer MJ, Powers VC, Wu JJ, Umansky SR, Tomei LD, Barr PJ. Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak. Nature 1995;374(6524):736–739

    PubMed  CAS  Google Scholar 

  82. Knudson CM, Tung KS, Tourtellotte WG, Brown GA, Korsmeyer SJ. Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 1995;270(5233):96–99

    PubMed  CAS  Google Scholar 

  83. Borner C, Martinou I, Mattmann C, Irmler M, Schaerer E, Martinou JC, Tschopp J. The protein bcl-2 alpha does not require membrane attachment, but two conserved domains to suppress apoptosis. J Cell Biol 1994;126(4):1059–1068

    PubMed  CAS  Google Scholar 

  84. Wang HG, Rapp UR, Reed JC. Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell 1996;87(4):629–638

    PubMed  CAS  Google Scholar 

  85. Yang E, Zha J, Jockei J, Boise LH, Thompson CB, Korsmeyer SJ. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell 1995;80(2):285–291

    PubMed  CAS  Google Scholar 

  86. Zha J, Harada H, Yang E, Jockei J, Korsmeyer SJ. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X. Cell 1996;87(4):619–628

    PubMed  CAS  Google Scholar 

  87. Muslin AJ, Tanner JW, Allen PM, Shaw AS. Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell 1996;84(6):889–897

    PubMed  CAS  Google Scholar 

  88. Gajewski TF, Thompson CB. Apoptosis meets signal transduction: elimination of a BAD influence. Cell 1996;87(4):589–592

    PubMed  CAS  Google Scholar 

  89. Wang HG, Takayama S, Rapp UR, Reed JC. Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1. Proc Natl Acad Sci USA 1996;93(14):7063–7068

    PubMed  CAS  Google Scholar 

  90. Shibasaki F, McKeon F. Calcineurin functions in Ca(2+)-activated cell death in mammalian cells. J Cell Biol 1995;131(3):735–743

    PubMed  CAS  Google Scholar 

  91. Linette GP, Li Y, Roth K, Korsmeyer SJ. Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation. Proc Natl Acad Sci USA 1996;93(18):9545–9552

    PubMed  CAS  Google Scholar 

  92. Pietenpol JA, Papadopoulos N, Markowitz S, Willson JK, Kinzler KW, Vogelstein B. Paradoxical inhibition of solid tumor cell growth by bcl2. Cancer Res 1994;54(14):3714–3717

    PubMed  CAS  Google Scholar 

  93. Vaux DL, Cory S, Adams JM. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 1988;335(6189):440–442

    PubMed  CAS  Google Scholar 

  94. Marvel J, Perkins GR, Lopez Rivas A, Collins MK. Growth factor starvation of bcl-2 overexpressing murine bone marrow cells induced refractoriness to IL-3 stimulation of proliferation. Oncogene 1994;9(4):1117–1122

    PubMed  CAS  Google Scholar 

  95. Linette GP, Hess JL, Sentman CL, Korsmeyer SJ. Peripheral T-cell lymphoma in lckpr-bcl-2 transgenic mice. Blood 1995;86(4):1255–1260

    PubMed  CAS  Google Scholar 

  96. Mazel S, Burtrum D, Petrie HT. Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death. J Exp Med 1996;183(5):2219–2226

    PubMed  CAS  Google Scholar 

  97. O’Reilly LA, Huang DC, Strasser A. The cell death inhibitor Bcl-2 and its homologues influence control of cell cycle entry. EMBO J 1996;15(24):6979–6990

    PubMed  Google Scholar 

  98. Vairo G, Innes KM, Adams JM. Bcl-2 has a cell cycle inhibitory function separable from its enhancement of cell survival. Oncogene 1996;13(7):1511–1519

    PubMed  CAS  Google Scholar 

  99. Huang DC, O’Reilly LA, Strasser A, Cory S. The anti-apoptosis function of Bcl-2 can be genetically separated from its inhibitory effect on cell cycle entry. EMBO J 1997;16(15):4628–4638

    PubMed  CAS  Google Scholar 

  100. Cleary M, Rosenberg SA. The bcl-2 gene, follicular lymphoma, and Hodgkin’s disease [editorial;comment]. J Natl Cancer Inst 1990;82(10):808–809

    PubMed  CAS  Google Scholar 

  101. Lipponen P, Pietilainen T, Kosma VM, Aaltomaa S, Eskelinen M, Syrjanen K. Apoptosis suppressing protein bcl-2 is expressed in well-differentiated breast carcinomas with favourable prognosis. J Pathol 1995;177(1):49–55

    PubMed  CAS  Google Scholar 

  102. Konopleva M, Zhao S, Jiang S, Snell V, Zhang X, Reed JC, Andreeff M. The antiapoptotic genes Bcl-XL and Bcl-2 are overexpressed in quiescent leukemic progenitor cells. Blood (Suppl 1) 1997;90:558a

    Google Scholar 

  103. Deng G, Lane C, Kornblau S, Goodacre A, Snell V, Andreeff M, Deisseroth AB. Ratio of bcl-xshort to bcl-xlong is different in good-and poor-prognosis subsets of acute myeloid leukemia. Mol Med 1998;4(3):158–164

    PubMed  CAS  Google Scholar 

  104. del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 1997;278(5338):687–689

    PubMed  Google Scholar 

  105. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997;91(2):231–241

    PubMed  CAS  Google Scholar 

  106. Haldar S, Jena N, Croce CM. Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci USA 1995;92(10):4507–4511

    PubMed  CAS  Google Scholar 

  107. Srivastava RK, Srivastava AR, Korsmeyer SJ, Nesterova M, Cho-Chung YS, Longo DL. Involvement of microtubules in the regulation of bcl2 phosphorylation and apoptosis through cyclic AMP-dependent protein kinase. Mol Cell Biol 1998;18(6):3509–3517

    PubMed  CAS  Google Scholar 

  108. Haldar S, Basu A, Croce CM. Bcl2 is the guardian of microtubule integrity. Cancer Res 1997;57(2):229–233

    PubMed  CAS  Google Scholar 

  109. Chang BS, Minn AJ, Muchmore SW, Fesik SW, Thompson CB. Identification of a novel regulatory domain in Bcl-X(L) and Bcl-2. EMBO J 1997;16(5):968–977

    PubMed  CAS  Google Scholar 

  110. May WS, Tyler PG, Ito T, Armstrong DK, Qatsha KA, Davidson NE. Interleukin-3 and bryostatin-1 mediate hyperphosphorylation of BCL2 alpha in association with suppression of apoptosis. J Biol Chem 1994;269(43):26865–26870

    PubMed  CAS  Google Scholar 

  111. Chen CY, Faller DV. Direction of p21 ras-generated signals towards cell growth or apoptosis is determined by protein kinase C and Bcl-2. Oncogene 1995;11(8):1487–1498

    PubMed  CAS  Google Scholar 

  112. Cheng EH, Levine B, Boise LH, Thompson CB, Hardwick JM. Bax-independent inhibition of apoptosis by Bcl-XL. Nature 1996;379(6565):554–556

    PubMed  CAS  Google Scholar 

  113. Strack PR, Frey MW, Rizzo CJ, Cordova B, George HJ, Meade R, Ho SP, Corman J, Tritch R, Korant BD. Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2. Proc Natl Acad Sci USA 1996;93(18):9571–9576

    PubMed  CAS  Google Scholar 

  114. Cheng EH, Kirsch DG, Clem RJ, Ravi R, Kastan MB, Bedi A, Ueno K, Hardwick JM. Conversion of Bcl-2 to a Bax-like death effector by caspases. Science 1997;278(5345):1966–1968

    PubMed  CAS  Google Scholar 

  115. Clem RJ, Cheng EH, Karp CL, Kirsch DG, Ueno K, Takahashi A, Kastan MB, Griffin DE, Earnshaw WC, Veliuona MA, Hardwick JM. Modulation of cell death by Bcl-XL through caspase interaction. Proc Natl Acad Sci USA 1998;95(2):554–559

    PubMed  CAS  Google Scholar 

  116. Reed JC. Double identity for proteins of the Bcl-2 family. Nature 1997;387(6635):773–776

    PubMed  CAS  Google Scholar 

  117. Minn AJ, Velez P, Schendel SL, Liang H, Muchmore SW, Fesik SW, Fill M, Thompson CB. Bcl-x(L) forms an ion channel in synthetic lipid membranes. Nature 1997;385(6614):353–357

    PubMed  CAS  Google Scholar 

  118. Schendel SL, Xie Z, Montai MO, Matsuyama S, Montai M, Reed JC. Channel formation by antiapoptotic protein Bcl-2. Proc Natl Acad Sci USA 1997;94(10):5113–5118

    PubMed  CAS  Google Scholar 

  119. Krajewski S, Tanaka S, Takayama S, Schibler MJ, Fenton W, Reed JC. Investigation of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes. Cancer Res 1993;53(19):4701–4714

    PubMed  CAS  Google Scholar 

  120. Gonzalez-Garcia M, Perez-Ballestero R, Ding L, Duan L, Boise LH, Thompson CB, Nunez G. bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria. Development 1994;120(10):3033–3042

    PubMed  CAS  Google Scholar 

  121. Yang T, Kozopas KM, Craig RW. The intracellular distribution and pattern of expression of Mcl-1 overlap with, but are not identical to, those of Bcl-2. J Cell Biol 1995;128(6):1173–1184

    PubMed  CAS  Google Scholar 

  122. Zamzami N, Susin SA, Marchetti P, Hirsch T, Gomez-Monterrey I, Castedo M, Kroemer G. Mitochondrial control of nuclear apoptosis [see comments]. J Exp Med 1996;183(4):1533–1544

    PubMed  CAS  Google Scholar 

  123. Liu X, Kim CN, Yang J, Jemmerson R, Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 1996;86(1):147–157

    PubMed  CAS  Google Scholar 

  124. Susin SA, Zamzami N, Castedo M, Hirsch T, Marchetti P, Macho A, Daugas E, Geuskens M, Kroemer G. Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J Exp Med 1996;184(4):1331–1341

    PubMed  CAS  Google Scholar 

  125. Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 1997;275(5303):1132–1136

    PubMed  CAS  Google Scholar 

  126. Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 1997;275(5303):1129–1132

    PubMed  CAS  Google Scholar 

  127. Marzo I, Brenner C, Zamzami N, Susin SA, Beutner G, Brdiczka D, Remy R, Xie ZH, Reed JC, Kroemer G. The permeability transition pore complex: a target for apoptosis regulation by caspases and bcl-2-related proteins. J Exp Med 1998;187(8):1261–1271

    PubMed  CAS  Google Scholar 

  128. Marzo I, Susin SA, Petit PX, Ravagnan L, Brenner C, Larochette N, Zamzami N, Kroemer G. Caspases disrupt mitochondrial membrane barrier function. FEBS Lett 1998;427(2):198–202

    PubMed  CAS  Google Scholar 

  129. Shaham S, Horvitz HR. Developing Caenorhabditis elegans neurons may contain both cell-death protective and killer activities. Genes Dev 1996;10(5):578–591

    PubMed  CAS  Google Scholar 

  130. Shaham S, Horvitz HR. An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death inhibitor. Cell 1996;86(2):201–208

    PubMed  CAS  Google Scholar 

  131. Chinnaiyan AM, O’Rourke K, Lane BR, Dixit VM. Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death. Science 1997;275(5303):1122–1126

    PubMed  CAS  Google Scholar 

  132. Irmler M, Hofmann K, Vaux D, Tschopp J. Direct physical interaction between the Caenorhabditis elegans ‘death proteins’ CED-3 and CED-4. FEBS Letters 1997;406(1-2):189–190

    PubMed  CAS  Google Scholar 

  133. Hofmann K, Bucher P, Tschopp J. The CARD domain: a new apoptotic signalling motif. Trends Biochem Sci 1997;22(5):155–156

    PubMed  CAS  Google Scholar 

  134. Spector MS, Desnoyers S, Hoeppner DJ, Hengartner MO. Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature 1997;385(6617):653–656

    PubMed  CAS  Google Scholar 

  135. Wu D, Wallen HD, Nunez G. Interaction and regulation of subcellular localization of CED-4 by CED-9. Science 1997;275(5303):1126–1129

    PubMed  CAS  Google Scholar 

  136. Hu Y, Benedict MA, Wu D, Inohara N, Nunez G. Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation. Proc Natl Acad Sci USA 1998;95:4386–4391

    PubMed  CAS  Google Scholar 

  137. Zou H, Henzel WJ, Liu X, Lutschg A, Wang X. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 1997;90(3):405–413

    PubMed  CAS  Google Scholar 

  138. Vaux DL. CED-4—the third horseman of apoptosis. Cell 1997;90(3):389–390

    PubMed  CAS  Google Scholar 

  139. Conradt B, Horvitz HR. The C. elegans protein EGL-1 is required for programmed cell death and interacts with the bcl-2-like protein CED-9. Cell 1998;93:519–529

    PubMed  CAS  Google Scholar 

  140. Duckett CS, Nava VE, Gedrich RW, Clem RJ, Van Dongen JL, Gilfillan MC, Shiels H, Hardwick JM, Thompson CB. A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J 1996;15(11):2685–2694

    PubMed  CAS  Google Scholar 

  141. Clem RJ, Miller LK. Control of programmed cell death by the baculovirus genes p35 and iap. Mol Cell Biol 1994;14(8):5212–5222

    PubMed  CAS  Google Scholar 

  142. Roy N, Mahadevan MS, McLean M, Shutler G, Yaraghi Z, Farahani R, Baird S, Besner-Johnston A, Lefebvre C, Kang X, et al. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 1995;80(4):167–178

    PubMed  CAS  Google Scholar 

  143. Rothe M, Pan MG, Henzel WJ, Ayres TM, Goeddel DV. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell 1995;83(7):1243–1252

    PubMed  CAS  Google Scholar 

  144. Uren AG, Pakusch M, Hawkins CJ, Puls KL, Vaux DL. Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. Proc Natl Acad Sci USA 1996;93(10):4974–4978

    PubMed  CAS  Google Scholar 

  145. Hay BA, Wassarman DA, Rubin GM. Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death. Cell 1995;83(7):1253–1262

    PubMed  CAS  Google Scholar 

  146. Deveraux QL, Takahashi R, Salvesen GS, Reed JC. X-linked IAP is a direct inhibitor of cell-death proteases. Nature 1997;388(6639):300–304

    PubMed  CAS  Google Scholar 

  147. Lovering R, Hanson IM, Borden KL, Martin S, O’Reilly NJ, Evan GI, Rahman D, Pappin DJ, Trowsdale J, Freemont PS. Identification and preliminary characterization of a protein motif related to the zinc finger. Proc Natl Acad Sci USA 1993;90(6):2112–2116

    PubMed  CAS  Google Scholar 

  148. Blake TJ, Shapiro M, Morse HC 3d, Langdon WY. The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif. Oncogene 1991;6(4):653–657

    PubMed  CAS  Google Scholar 

  149. de The H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A. The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell 1991;66(4):675–684

    PubMed  Google Scholar 

  150. Song HY, Donner DB. Association of a RING finger protein with the cytoplasmic domain of the human type-2 tumour necrosis factor receptor. Biochem J 1995;309(Pt 3):825–829

    PubMed  CAS  Google Scholar 

  151. Hu HM, O’Rourke K, Boguski MS, Dixit VM. A novel RING finger protein interacts with the cytoplasmic domain of CD40. J Biol Chem 1994;269(48):30069–30072

    PubMed  CAS  Google Scholar 

  152. Cheng G, Cleary AM, Ye ZS, Hong DI, Lederman S, Baltimore D. Involvement of CRAF1, a relative of TRAF, in CD40 signaling. Science 1995;267(5203):1494–1498

    PubMed  CAS  Google Scholar 

  153. Sato T, Irie S, Reed JC. A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40. FEBS Letters 1995;358(2):113–118

    PubMed  CAS  Google Scholar 

  154. Borden KL, Boddy MN, Lally J, O’Reilly NJ, Martin S, Howe K, Solomon E, Freemont PS. The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBOJ 1995;14(7):1532–1541

    CAS  Google Scholar 

  155. Takahashi R, Deveraux Q, Tamm I, Welsh K, Assa-Munt N, Salvesen GS, Reed JC. A single BIR domain of XIAP sufficient for inhibiting caspases. J Biol Chem 1998;273(14):7787–7790

    PubMed  CAS  Google Scholar 

  156. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997;3(8):917–921

    PubMed  CAS  Google Scholar 

  157. Adida C, Crotty PL, McGrath J, Berrebi D, Diebold J, Altieri DC. Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol 1998;152(1):43–49

    PubMed  CAS  Google Scholar 

  158. Keith FJ, Bradbury DA, Yong-Ming Z, Russel NH. Inhibition of bcl-2 with antisense oligonucleotides induces apoptosis and increases the sensitivity of AML blasts to Ara-C. Leukemia 1995;9:131–138

    PubMed  CAS  Google Scholar 

  159. Konopleva M, Tari A, López-Berestein A, Andreeff M. Inhibition of Bcl-2 with liposomal-delivered antisense oligonucleotides (AS-ODN) induces apoptosis and increases the sensitivity of primary acute myeloid leukemia (AML) cells and cell lines to cytosine arabinoside and doxorubicin. Blood 1997(Suppl l);90:10, 494a

    Google Scholar 

  160. Webb A, Cunningham D, Cotter F, Clarke PA, Stefano PA, Ross P, Corbo M, Dziewanowska Z. Bcl-2 antisense therapy in patients with non-Hodgkin’s lymphoma. The Lancet 1997;349:1137–1141

    CAS  Google Scholar 

  161. Andreeff M, Jiang S, Zhang X, Konopleva M, Estrov Z, Snell VE, Xie Z, Okcu MF, Sanchez-Williams G, Dong J, Estey EH, Champlin RE, Kornblau SM, Reed JC, Zhao S. Expression of bcl-2-related genes in normal and AML progenitors: changes induced by chemotherapy and retinoic acid. Leukemia 1999; in press

    Google Scholar 

  162. McCullogh EA. Phosphorylation of bcl-2 after exposure of human leukemic cells to retinoic acid. Blood (Suppl1)1997;90:494a

    Google Scholar 

  163. Piche A, Grim J, Rancourt C, Gomez-Navarro J, Reed JC, Curiel DT. Modulation of bcl-2 protein levels by an intracellular anti-bcl-2 single-chain antibody increases drug-induced cytotoxicity in the breast cancer cell line MCF-7. Cancer Res 1998;58:2134–2140

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Hematology and Therapy, M.D. Anderson Cancer Center The University of Texas, Houston, Texas, USA

    Marina Konopleva, Shourong Zhao, Zhong Xie, Harry Segall, David F. Claxton, Steven M. Kornblau & Michael Andreeff M.D., Ph.D.

  2. Department of Bioimmunotherapy, M.D. Anderson Cancer Center The University of Texas, Houston, Texas, USA

    Zeev Estrov

  3. Department of Lymphoma Division of Medicine, M.D. Anderson Cancer Center The University of Texas, Houston, Texas, USA

    Anas Younes

  4. Department of Molecular Hematology and Therapy, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 81, Houston, Texas, 77030, USA

    Michael Andreeff M.D., Ph.D.

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  1. Marina Konopleva
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  1. University Hospital Vrije Universiteit, Amsterdam, The Netherlands

    G. J. L. Kaspers , R. Pieters  & A. J. P. Veerman ,  & 

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Konopleva, M. et al. (1999). Apoptosis. In: Kaspers, G.J.L., Pieters, R., Veerman, A.J.P. (eds) Drug Resistance in Leukemia and Lymphoma III. Advances in Experimental Medicine and Biology, vol 457. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4811-9_24

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