Abstract
The protease responsible for the cleavage of poly(ADP-ribose) polymerase and necessary for apoptosis has been purified and characterized. This enzyme, named apopain, is composed of two subunits of relative molecular mass (Mr) 17K and 12K that are derived from a common proenzyme identified as CPP32. This proenzyme is related to interleukin-lβ-converting enzyme (ICE) and CED-3, the product of a gene required for programmed cell death in Caenorhabditis elegans. A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death.
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References
Kerr, J. F., Wyllie, A. H. & Currie, A. R. Br. J. Cancer 26, 239–257 (1972).
Martin, S. J., Green, D. R. & Cotter, T. G. Trends biochem. Sci. 19, 26–30 (1994).
Barr, P. J. & Tomei, L. D. Biotechnology 12, 487–493 (1994).
Carson, D. A. & Ribeiro, J. M. Lancet 341, 1251–1254 (1994).
Ellis, R. E., Yuan, J. & Horvitz, H. R. A. Rev. Cell Biol. 7, 663–698 (1991).
Yuan, J., Shaham, S., Ledoux, S., Ellis, J. M. & Horvitz, J. R. Cell 75, 641–652 (1993).
Thornberry, N. A. et al. Nature 356, 768–774 (1992).
Cerretti, D. P. et al. Science 256, 97–100 (1992).
Miura, M., Zhu, H., Rotello, R., Hartwieg, E. A. & Yuan, J. Cell 78, 653–660 (1993).
Gagliardini, V. et al. Science 263, 826–828 (1994).
Juarez-Salinas, H., Sims, J. L. & Jacobson, M. K. Nature 282, 740–741 (1979).
Berger, N. A., Sikorski, G. W., Petzold, S. J. & Kurohara, K. K. Biochemistry 19, 289–293 (1980).
Satoh, M. S. & Lindahl, T. Nature 356, 356–358 (1992).
Ding, R., Pommier, Y., Kang, V. H. & Smulson, M. J. biol. Chem. 267, 12804–12812 (1992).
Smulson, M., Istock, N., Ding, R. & Cherney, B. Biochemistry 33, 6186–6194 (1994).
Ding, R. & Smulson, M. Cancer Res. 54, 4627–4634 (1994).
Burkle, A., Grube, K. & Küpper, J.-H. Expl clin. Immunogenet. 9, 230–240 (1992).
Wang, Z. Q. et al. Genes Dev. 9, 509–520 (1995).
Kaufmann, S. H., Desnoyers, S., Ottaviano, Y., Davidson, N. E. & Poirier, G. G. Cancer Res. 53, 3976–3985 (1993).
Lazebnik, Y. A., Kaufmann, S. H., Desnoyers, S., Poirier, G. G. & Earnshaw, W. C. Nature 371, 346–347 (1994).
Yoshihara, K., Tanigawa, Y. & Koide, S. S. Biochem. biophys. Res. Commun. 59, 658–665 (1974).
Yoshihara, K., Tanigawa, Y., Burzio, L. & Koide, S. S. Proc. natn. Acad. Sci. U.S.A. 72, 289–293 (1975).
Tanaka, Y., Yoshihara, K., Itaya, A., Kamiya, T. & Koide, S. S. J. biol. Chem. 259, 6579–6585 (1984).
Kumar, S., Kinoshita, M., Noda, M., Copeland, N. G. & Jenkins, N. A. Genes Dev. 8, 1613–1626 (1994).
Wang, L., Miura, M., Bergeron, L., Zhu, J. & Yuan, J. Cell 78, 739–750 (1994).
Fernandes-Alnemri, T., Litwack, G. & Alnemri, E. S. J. biol. Chem. 269, 30761–30764 (1994).
Munday, N. A. et al. J. biol. Chem. 270, 15870–15876 (1995).
Williams, M. S. & HenKart, P. A. J. Immun. 153, 4247–4255 (1994).
Heusel, J. W., Wesselschmidt, R. L., Shresta, S., Russell, J. H. & Ley, T. J. Cell 76, 977–987 (1994).
Li, P. et al. Cell 80, 401–411 (1995).
Kuida, K. et al. Science 267, 2000–2003 (1995).
Enari, M., Hug, H. & Nagata, S. Nature 375, 78–81 (1995).
Los, M. et al. Nature 375, 81–83 (1995).
Ayala, J. M. et al. J. Immun. 153, 2592–2599 (1994).
Ray, C. A. et al. Cell 69, 597–604 (1992).
Howard, A. D. et al. J. Immun. 154, 2321–2332 (1995).
Wilson, K. P. et al. Nature 370, 270–275 (1994).
Walker, N. P. C. et al. Cell 78, 343–352 (1994).
Westerik, J. O. & Wolfenden, R. J. biol. Chem. 247, 8195–8197 (1972).
Solary, E., Bertrand, R., Kohn, K. W. & Pommier, Y. Blood 81, 1359–1368 (1993).
Lazebnik, Y. A., Cole, S., Cooke, C. A., Nelson, W. G. & Earnshaw, W. C. J. Cell Biol. 123, 7–22 (1993).
deMurcia, G., Ménissier-deMurcia, J. & Schreiber, V. BioEssays 13, 455–462 (1991).
Langlois, A. J., Lapis, K., Ishizaki, R., Beard, J. W. & Bolognesi, D. P. Cancer Res. 34, 1457–1464 (1974).
Cherney, B. W. et al. Proc. natn. Acad. Sci. U.S.A. 84, 8370–8374 (1987).
Chapman, K. T. Bioorg. Med. Chem. Lett. 2, 613–618 (1992).
Miller, D. K. et al. J. biol. Chem. 268, 18062–18069 (1993).
Devereux, J., Haeberli, P. & Smithies, O. Nucleic Acids Res. 12, 387–395 (1984).
Morrison, J. F. Trends biochem. Sci. 7, 102–105 (1982).
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Nicholson, D., Ali, A., Thornberry, N. et al. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376, 37–43 (1995). https://doi.org/10.1038/376037a0
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DOI: https://doi.org/10.1038/376037a0
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