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Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE

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Abstract

RECENT studies suggest that pro teases of the inter leukin 1-β-con-verting enzyme (ICE)/ced-3 family are involved in initiating the active phase of apoptosis1–3. Here we identify a novel protease resembling ICE (prICE) that is active in a cell-free system that reproduces the morphological and biochemical events of apoptosis4. prICE cleaves the nuclear enzyme poly(ADP-ribose) polymerase (PARP) at a tetrapeptide sequence identical to one of two ICE sites in pro-inter leu kin-l-β. However, prICE does not cleave purified pro-interleukin- 1-β, and purified ICE does not cleave PARP, indicating that the two activities are distinct. Inhibition of prICE abolishes all manifestations of apoptosis in the extracts including morphological changes, cleavage of PARP and production of an oligonucleosomal ladder. These studies suggest that prICE might be pivotal in initiating the active phase of apoptosis in vitro and in intact cells.

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References

  1. Yuan, J., Shaham, S., Ledoux, S., Ellis, H. M. & Horvitz, H. R. Cell 75, 641–652 (1993).

    Article  CAS  Google Scholar 

  2. Gagliardini, V. et al. Science 263, 826–828 (1994).

    Article  CAS  ADS  Google Scholar 

  3. Miura, M., Zhu, H., Rotello, R., Hartweig, E. A. & Yuan, J. Cell 75, 653–660 (1993).

    Article  CAS  Google Scholar 

  4. Lazebnik, Y. A., Cole, S., Cooke, C. A., Nelson, W. G. & Earnshaw, W. C. J. Cell Biol. 123, 7–22 (1993).

    Article  CAS  Google Scholar 

  5. Kaufmann, S. H., Desnoyers, S., Ottaviano, Y., Davidson, N. E. & Poirier, G. G. Cancer Res. 53, 3976–3985 (1993).

    CAS  PubMed  Google Scholar 

  6. Boy de la Tour, E. & Laemmli, U. K. Cell 55, 937–944 (1988).

    Article  CAS  Google Scholar 

  7. Saitoh, H. et al. Cell 70, 115–125 (1992).

    Article  CAS  Google Scholar 

  8. Ohtsubo, M. et al. Genes Dev. 1, 585–593 (1987).

    Article  CAS  Google Scholar 

  9. Cherney, B. W. et al. Proc. natn. Acad. Sci. U.S.A. 84, 8370–8374 (1987).

    Article  CAS  ADS  Google Scholar 

  10. Saito, I., Hatakeyama, K., Kido, T., Ohkubo, H., Nakanishi, S. & Ueda, K. Gene 90, 249–254 (1990).

    Article  CAS  Google Scholar 

  11. Ittel, M.-E., Garnier, J.-M., Jeltsch, J.-M. & Niedergang, C. P. Gene 102, 157–164 (1991).

    Article  CAS  Google Scholar 

  12. Odake, S. et al. Biochemistry 30, 2217–2227 (1991).

    Article  CAS  Google Scholar 

  13. Shi, L., Kraut, R. P., Aebersold, R. & Greenberg, A. H. J. exp. Med. 175, 553–566 (1992).

    Article  CAS  Google Scholar 

  14. Heusel, J. W., Wesselschmidt, R. L., Shresta, S., Russel, J. H. & Ley, T. J. Cell 76, 977–987 (1994).

    Article  CAS  Google Scholar 

  15. Howard, A. D. et al. J. Immun. 147, 2964–2969 (1991).

    CAS  Google Scholar 

  16. Thornberry, N. A. et al. Nature 356, 768–774 (1992).

    Article  CAS  ADS  Google Scholar 

  17. Black, R. A., Kronheim, S. R. & Sleath, P. R. FEBS Lett. 247, 386–390 (1989).

    Article  CAS  Google Scholar 

  18. Wyllie, A. H., Morris, R. G., Smith, A. L. & Dunlop, D. J. Path. 142, 67–77 (1984).

    Article  CAS  Google Scholar 

  19. Kaufmann, S. H. Cancer Res. 49, 5870–5878 (1989).

    CAS  PubMed  Google Scholar 

  20. Ellis, R. E., Yuan, J. & Horvitz, H. R. A. Rev. Cell Biol. 7, 663–698 (1991).

    Article  CAS  Google Scholar 

  21. Lamarre, D. et al. Biochim. biophys. Acta 950, 147–160 (1988).

    Article  CAS  Google Scholar 

  22. Huletsky, A. et al. J. biol. Chem. 265, 8878–8886 (1989).

    Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology and Anatomy, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205, USA

    Y. A. Lazebnik & W. C. Earnshaw

  2. Department of Oncology, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205, USA

    S. H. Kaufmann

  3. Department of Pharmacology, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205, USA

    S. H. Kaufmann

  4. Poly(ADP-Ribose) Metabolism Group, Department of Molecular Endocrinology, Centre Hospitalier de I'Université Laval Research Center and Laval University, Sainte-Foy, Quebec, Canada, G1V 4G2

    S. Desnoyers & G. G. Poirier

Authors
  1. Y. A. Lazebnik
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  2. S. H. Kaufmann
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  3. S. Desnoyers
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  4. G. G. Poirier
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  5. W. C. Earnshaw
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Lazebnik, Y., Kaufmann, S., Desnoyers, S. et al. Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371, 346–347 (1994). https://doi.org/10.1038/371346a0

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  • DOI: https://doi.org/10.1038/371346a0

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