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Anti-apoptosis engineering

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Abstract

An increased understanding of apoptosis makes anti-apoptosis engineering possible, which is an approach used to inhibit apoptosis for the purpose of therapeutic, or industrial applications in the treatment of the diseases associated with increased apoptosis, or to improve the productivity of animal cell cultures, respectively. Some known anti-apoptotic proteins are the Bcl-2 family, IAP (inhibitor of apoptosis) and Hsps (heat shock proteins), with which anti-apoptosis engineering has progressed. This article reviews anti-apoptosis engineering using known anti-apoptotic compounds, and introduces a 30 K protein, isolated from silkworm hemolymph, as a novel anti-apoptotic protein, that shows no homology with other known anti-apoptotic proteins. The regulation of apoptosis, using anti-apoptotic proteins and genes originating from the silkworm,Bombyx mori, may provide a new strategy in this field.

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References

  1. Walker, N. I., B. V. Harmon, G. C. Gobe, and J. F. R. Kerr (1988) Patterns of cell death.Methods Archive Exp. Pathol. 13: 18–54.

    CAS  Google Scholar 

  2. Wyllie, A. H., R. G. Morris, A. L. Smith, and D. Dunlop (1984) Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesis.J. Pathol. 142: 66–77.

    Article  Google Scholar 

  3. Wyllie, A. H., J. F. R. Kerr, and A. R. Currie (1980). Cell death: the significance of apoptosis.Int. Rev. Cytol. 68: 251–306.

    Article  CAS  Google Scholar 

  4. Ellis, R. E., J. Yuan, and H. R. Horvitz (1991) Mechanisms and functions of cell death.Annu. Rev. Cell Biol. 7: 663–698.

    Article  CAS  Google Scholar 

  5. Raff, M. C., B. A. Barres, J. F. Burne, H. S. Coles, Y. Ishizaki, and M. D. Jacobson (1993) Programmed cell death and the control of cell survival: Lessons from nervous system.Science 262: 695–700.

    Article  CAS  Google Scholar 

  6. Glucksmann, A. (1950) Cell death in normal vertebrated ontogeny.Bio. Rev. Cambridge Phil. Soc. 26: 59–86.

    Article  Google Scholar 

  7. Kerr, J. F. R., A. H. Wyllie, and A. H. Currie (1972) Apoptosis: A basic biological phenomenon with wide-randing implications in tissue kinetics.Br. J. Cancer 26: 239–257.

    CAS  Google Scholar 

  8. Lenardo, M. J. (1997) Introduction: The molecular regulation of lymphocyte apoptosis.semin. Immunol. 9: 1–5.

    Article  CAS  Google Scholar 

  9. Yuan, J.-Y. and R. H. Horvitz (1990) Genetic mosaic analysis of ced-3 and ced-4, two genes that control programmed cell death in the nematode C. elegans.Dev. Biol. 138: 33–41.

    Article  CAS  Google Scholar 

  10. Hengartner, M. O., R. E. Ellis, and R. H. Horvitz (1992)Caenorhabditis elegans gene ced-9 protects cells from programmed cell death.Nature 356: 494–499.

    Article  CAS  Google Scholar 

  11. Hengartner, M. O. and R. H. Horvitz (1994) C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2.Cell 76: 665–676.

    Article  CAS  Google Scholar 

  12. Yuan, J.-Y., S. Shaham, S. Ledoux, M. H. Ellis, and R. H. Horvitz (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β converting enzyme.Cell 75: 641–652.

    Article  CAS  Google Scholar 

  13. Chinnaiyan, A. M., K. O’Rourke, B. R. Lane, and V. M. Dixit (1997) Interaction of CED-4 with CED-3 and CED-9: A molecular framework for cell death.Science 275: 1122–1126.

    Article  CAS  Google Scholar 

  14. Zou, H., W. J. Henzel, X. Liu, A. Lutschg, and X. Wang (1997) Apaf-1, a human protein homologous toC. elegans CED-4, participates in cytochrome c-dependent activation of capases-3.Cell 90: 405–413.

    Article  CAS  Google Scholar 

  15. Tewari, M., L. Quan, K. O’Rourke, S. Desonoyers, Z. Zeng, D. R. Beidler, G. C. Poirier, G. S. Salvesen, and V. M. Dixit (1995) Yama/CPP32β, a mammalian homolog of ced-3, is a CrmA-inhibitable protease that cleaves the death substrate poly (ADP-ribose) polymerase.Cell 81: 801–809.

    Article  CAS  Google Scholar 

  16. Clem, R. J., M. Fechheimer, and L. K. Miller (1991) Prevention of apoptosis by a baculovirus gene during infection of insect cells.Science 254: 1388–1390.

    Article  CAS  Google Scholar 

  17. Fraser, A. and G. Evan (1996) A license to kill.Cell 85: 781–784.

    Article  CAS  Google Scholar 

  18. Mastrangelo, A. J. and M. J. Betenbaugh (1998) Overcoming apoptosis: New methods for improving protein-expression systems. Trends Biotechnol. 16: 88–95.

    Article  CAS  Google Scholar 

  19. Susin, S. A., N. Zamzami, and G. Kroemer (1998) Mitochondria as a regulator of apoptosis—doubt no more.Biochim. Biophysis. Acta 1366: 151–165.

    Article  CAS  Google Scholar 

  20. Liu, X., C. N. Kim, J. Yang, and X. Wang (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c.Cell 86: 147–157.

    Article  CAS  Google Scholar 

  21. Srinivasula, S.M., M. Ahmad, T. Fernandes-Alnemri, and E. S. Alnemri (1998) Autoactivation of pro-caspase-9 by Apaf-1-mediated oligomerization.Mol. Cell 1: 949–957.

    Article  CAS  Google Scholar 

  22. Schmitt, E., A.-T. Sane, and R. Bertrand (1999) Activation and role of caspases in chemocherapy-induced apoptosis.Drug Resist. Updat. 2: 21–29.

    Article  CAS  Google Scholar 

  23. Rosse, T., R. Olivier, L. Monney, M. Rager, S. Conus, I. Fellay, B. Jansen, and C. Borner (1998) Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c.Nature 391: 496–499.

    Article  CAS  Google Scholar 

  24. Stennicke, H. R., J. M. Jurgensmeier, and H. Shin (1998) Pro-caspase-3 is a major physiologic target of caspase-8.J. Biol. Chem. 273: 27084–27090.

    Article  CAS  Google Scholar 

  25. Tsujimoto, Y., J. Cossman, E. Jaff, and C. Croce (1985) Involvement of the bcl-2 gene in human follicular lymphoma.Science 228: 1440–1443.

    Article  CAS  Google Scholar 

  26. Hockenbery, D., G. Nunez, C. Milliman, R. D. Screiber, and S. Korsmeyer (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death.Nature 348: 334–336.

    Article  CAS  Google Scholar 

  27. Crook, N. E., R. J. Clem, and L. K. Miller (1993) An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif.J. Virol. 67: 2168–2174.

    CAS  Google Scholar 

  28. Birnbaum, M. J., R. J. Clem, and L. K. Miller (1994) An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motif.J. Virol. 68: 2521–2528.

    CAS  Google Scholar 

  29. Deveraux, O. L. and J. C. Reed (1999) IAP family proteins: Suppressor of apoptosis.Genes Dev. 13: 239–252.

    Article  CAS  Google Scholar 

  30. Deveraux, O. L., R. Takahashi, G. S. Salvesen, and J. C. Reed (1997) X-linked IAP is a direct inhibitor of cell-death proteases.Nature 388: 239–252.

    Article  Google Scholar 

  31. Roy, N., O. L. Deveraux, R. Takahashi, G. S. Salvesen, and J. C. Reed (1997) The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases.EMBO J. 16: 6914–6925.

    Article  CAS  Google Scholar 

  32. Tamm, I., Y. Wang, E. Sausville, D. A. Scudiero, N. Vigna, T. Oltersdorf, and J. C. Reed (1998) IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs.Cancer Res. 58: 5315–5320.

    CAS  Google Scholar 

  33. Deveraux, O. L., N. Roy, H. R. Stennicke, T. Van Arsdale, Q. Zhou, S. M. Srinivasula, E. S. Alnemri, G. S. Salvesen, and J. C. Reed (1998) IAP block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases.EMBO J. 17: 2215–2223.

    Article  CAS  Google Scholar 

  34. Rothe, M., M.-G. Pan, W. J. Henzel, T. M. Ayers, and D. V. Goeddel (1995) The TNFR2-TRAF signaling complex contains two novel proteins related to baculovirus inhibitor of apoptosis proteins.Cell 83: 1243–1252.

    Article  CAS  Google Scholar 

  35. Linquist, S. and E. A. Craig (1988) The heat shock proteins.Annu. Rev. Genet. 22: 631–677.

    Article  Google Scholar 

  36. Mckey, D. B. (1993) Structure and mechanism of 70-kDa heat-shock-related proteins.Adv. Protein Chem. 44: 67–97.

    Article  Google Scholar 

  37. Arrigo, A. P. (1998) Small stress proteins: Chaperones that act as regulators of intracellular redox state and programmed cell death.Biol. Chem. 379: 19–26.

    CAS  Google Scholar 

  38. Bukau, B. and A. L. Horwich (1998) The Hsp 70 and Hsp60 chaperone machines.Cell 92: 351–366.

    Article  CAS  Google Scholar 

  39. Jaattela, M., D. Wissing, P. A. Bauer, and G. C. Li (1998) Major heat shock protein hsp70 protects tumor cells from tumor necrosis factor cytotoxicity.EMBO J. 11: 3507–3512.

    Google Scholar 

  40. Jaattela, M., D. Wissing, K. Kokholm, T. Kallunki, and M. Egeblad (1998) Hsp70 exerts its anti-apoptotic function downstream of caspase-3-like proteases.EMBO J. 17: 6124–6134.

    Article  CAS  Google Scholar 

  41. Mehlen, P., C. Kretz-Remy, X. Preville, and A.-P. Arrigo (1996) Human hsp27,Drosophila hsp27 and human α-crystallin expression-mediated increase in glutathion is essential for the protective activity of these proteins against essential for the protective activity of these proteins against TNFα-induced cell death.EMBO J. 15: 2695–2706.

    CAS  Google Scholar 

  42. Thompson, C. B. (1995) Apoptosis in the pathogenesis and treatment of disease.Science 267: 1456–1462.

    Article  CAS  Google Scholar 

  43. Fadeel, B., S. Orrenius, and B. Zhivotovsky (1999) Apoptosis in human disease: A new skin for the old ceremony?Biochem. Biophys. Res. Commun. 266: 699–717.

    Article  CAS  Google Scholar 

  44. Ray, C. A., R. A. Black, S. R. Kronheim, T. A. Greenstreet, P. R. Sleath, G. S. Salvesen, and D. J. Pickup (1992) Viral inhibition of inflammation: Cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme.Cell 69: 597–604.

    Article  CAS  Google Scholar 

  45. Gagliardini, V., P. A. Fernandez, R. K. Lee, H. C. Drexler, R. J. Rotello, M. C. Fishman, and J. Yuan (1994) Prevention of vertebrate neuronal death by the crmA gene.Science 263: 826–828.

    Article  CAS  Google Scholar 

  46. Viswanath, V, Z. Wu, C. Fonck, O. Wei, R. Boonplueang, and J. K. Andersen (2000) Transgenic mice neuronally expressing baculoviral p35 are resistant to diverse types of induced apoptosis, including seizure-associated neurodegeneration.Proc. Natl. Acad. Sci. USA 97: 2270–2275.

    Article  CAS  Google Scholar 

  47. Hisahara, S., T. Araki, F. Sugiyama, K. Yagami, M. Suzuki, K. Abe, K. Yamamura, J. Miyazaki, T. Momoi, T. Saruta, C. C. Bernard, H. Okano, and M. Miura (2000) Targeted expression of baculovirus p35 caspase inhibitor in oligodendrocytes protects mice against autoimmune-mediated demyelination.EMBO J. 19: 341–348.

    Article  CAS  Google Scholar 

  48. Tran, J., J. Rak, C. Sheehan, S.D. Saibil, E. LaCasse, R. G. Korneluk, and R. S. Kerbel (1999) Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells.Biochem. Biophys. Res. Commun. 264: 781–788.

    Article  CAS  Google Scholar 

  49. Chung, J. D., C. Zabel, A. J. Sinskey, and G. Stephanopoulos (1997) Extension of Sp2/0 hybridoma cell viability through interleukin-6 supplementation.Biotechnol. Bioeng. 55: 439–446.

    Article  CAS  Google Scholar 

  50. Simpson, N. H., A. E. Milner, and M. Al-Rubeai (1997) Prevention of hybridoma cell death by bel-2 during suboptimal culture conditions.Biotechnol. Bioeng. 54: 1–16.

    Article  CAS  Google Scholar 

  51. Kim, N. S. and G. M. Lee (2000) Overexpression of bcl-2 inhibits sodium butyrate-induced apoptosis in Chinese hamster ovary cells resulting in enhanced humanized antibody production.Biotechnol. Bioeng. 71: 184–193.

    Article  CAS  Google Scholar 

  52. Kim, N. S. and G. M. Lee (2002) Inhibition of sodium butyrate-induced apoptosis in recombinant Chinese hamster ovary cells by constitutively expressing antisense RNA of caspase-3.Biotechnol. Bioeng. 78: 217–228.

    Article  CAS  Google Scholar 

  53. Mastrangelo, A. J., J. M. Hardwick, E. Bex, M. J. Betenbaugh (2000) Part I. Bcl-2 and Bcl-x(L) limit apoptosis upon infection with alphavirus vectors.Biotechnol. Bioeng. 67: 544–554.

    Article  CAS  Google Scholar 

  54. Mastrangelo, A. J., J. M. Hardwick, S. Zou, M. J. Betenbaugh (2000) Part II. Overexpression of bcl-2 family members enhances survival of mammalian cells in response to various culture insults.Biotechnol. Bioeng. 67: 555–564.

    Article  CAS  Google Scholar 

  55. Sauerwald, T. M., M. J. Betenbaugh, and G. A. Oyler (2002) Inhibiting apoptosis in mammalian cell culture using the caspase inhibitor XIAP and deletion mutants.Biotechnol. Bioeng. 77: 704–716.

    Article  CAS  Google Scholar 

  56. Lasunskaia, E. B., I. I. Fridlianskaia, Z. A. Darieva, M. S. Da Silva, M. M. Kanashiro, and B. A. Margulis (2003) Transfection of NSO myeloma fusion partner cells with HSP70 gene results in higher hybridoma yield by improving cellular resistance to apoptosis.Biotechnol. Bioeng. 81: 496–504.

    Article  CAS  Google Scholar 

  57. Mercille, S. and B. Massie (1999) Apoptosis-resistant E1B-19K-expressing NS/0 myeloma cells exhibit increased viability and chimeric antibody productivity under perfusion culture conditions.Biotechnol. Bioeng. 63: 529–543.

    Article  CAS  Google Scholar 

  58. Ha, S. H., T. H. Park, and S.-E. Kim (1996) Silkworm hemolymph as a substitute for fetal bovine serum in insect cell culture.Biotechnol. Tech. 10: 401–406.

    Article  CAS  Google Scholar 

  59. Kim, E. J., J.-Y. Choi, S.-E. Kim, and T. H. Park (1998) Oxidation-deficient silkworm hemolymph as a medium supplement for insect cell culture.Biotechnol. Bioprocess Eng. 3: 87–90.

    Article  Google Scholar 

  60. Kim, E. J. and T. H. Park (1999) Reduction of FBS concentration through adaptation process in mammalian cell culture and addition of silkworm hemolymph in insect cell culture.J. Microbiol. Biotechnol. 9: 227–229.

    Google Scholar 

  61. Ha, S. H. and T. H. Park (1997) Utilization of silkworm hemolymph for production of recombinant protein in an insect cell-baculovirus system.Biotechnol. Lett. 19: 1087–1091.

    Article  CAS  Google Scholar 

  62. Rhee, W. J., E. J. Kim, and T. H. Park (1999) Kinetic effect of silkworm hemolymph on the delayed host cell death in an insect cell-baculovirus system.Biotechnol. Prog. 15: 1028–1032.

    Article  CAS  Google Scholar 

  63. Rhee, W. J. and T. H. Park (2000) Silkworm hemolymph inhibits baculovirus-induced insect cell apoptosis.Biochem. Biophys. Res. Commun. 271: 186–190.

    Article  CAS  Google Scholar 

  64. Rhee, W. J. and T. H. Park (2001) Flow cytometric analysis of the effect of silkworm hemolymph on the baculovirus-induced insect cell apoptosis.J. Microbiol. Biotechnol. 11(5): 853–857.

    Google Scholar 

  65. Rhee, W. J., E. J. Kim, and T. H. Park (2002) Silkworm hemolymph as a potent inhibitor of apoptosis in Sf9 cells.Biochem. Biophys. Res. Commun. 295: 779–783.

    Article  CAS  Google Scholar 

  66. Choi, S. S., W. J. Rhee, and T. H. Park (2002) Inhibition of human cell apoptosis by silkworm hemolymph.Biotechnol. Prog. 18: 874–878.

    Article  CAS  Google Scholar 

  67. Kim, E. J., W. J. Rhee, and T. H. Park (2001) Isolation and characterization of an apoptosis-inhibiting component from the hemolymph ofBombyx mori.Biochem. Biophys. Res. Commun. 285: 224–228.

    Article  CAS  Google Scholar 

  68. Izumi, S., J. Fujie, S. Yamada, and S. Tomino (1981) Molecular properties and biosynthesis of major plasma proteins inBombyx mori.Biochim. Biophys. Acta 670: 222–229.

    CAS  Google Scholar 

  69. Mine, E., S. Izumi, M. Katsuki, and S. Tomino (1983) Development and sex-dependent regulation of storage protein synthesis in the silkworm,Bombyx mori.Develop. Biol. 97: 329–337.

    Article  CAS  Google Scholar 

  70. Sakai, N., S. Mori, S. Izumi, K. Haino-Fukushima, T. Ogura, H. Maekawa, and S. Tomino (1988) Structure and expression of mRNA coding for major plasma proteins ofBombyx mori.Biochim. Biophys. Acta 949: 224–232.

    CAS  Google Scholar 

  71. Kim, E. J. (2003)Isolation of a Novel Anti-apoptotic Protein from the Hemolymph of Bombyx moriand Its Application to Animal Cell Culture. Ph. D. Thesis, Seoul National University, Seoul, Korea.

    Google Scholar 

  72. Agathos, S. N. (1991) Production scale insect cell culture.Biotechnol. Adv. 9: 51–58.

    Article  CAS  Google Scholar 

  73. Miller, L. K. (1993) Baculoviruses: High level expression on insect cells.Curr. Opin. Genet. Dev. 3b: 97–101.

    Article  Google Scholar 

  74. Granados, R. R. and Y. Hashimoto (1983) Infectivity of baculovirus to cultured cells. pp. 489–542. In: J. Mitsuhashi, (ed.).Invertebrate Cell System. CRC press, Boca Raton, FL, USA.

    Google Scholar 

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  1. School of Chemical Engineering and Institute of Chemical Processes, Seoul National University, 151-744, Seoul, Korea

    Eun Jeong Kim & Tai Hyun Park

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Kim, E.J., Park, T.H. Anti-apoptosis engineering. Biotechnol Bioproc E 8, 76–82 (2003). https://doi.org/10.1007/BF02940260

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