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.
This is a preview of subscription content
Access options
Subscribe to Journal
Get full journal access for 1 year
$199.00
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Buy article
Get time limited or full article access on ReadCube.
$32.00
All prices are NET prices.
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).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/376037a0
Further reading
-
Anti-lipolysis-stimulated lipoprotein receptor monoclonal antibody as a novel therapeutic agent for endometrial cancer
BMC Cancer (2022)
-
Redefining the role of Ca2+-permeable channels in photoreceptor degeneration using diltiazem
Cell Death & Disease (2022)
-
Toxic effects of zinc oxide nanoparticles and histopathological and caspase-9 expression changes in the liver and lung tissues of male mice model
Applied Nanoscience (2022)
-
EGFR inhibitors switch keratinocytes from a proliferative to a differentiative phenotype affecting epidermal development and barrier function
BMC Cancer (2021)
-
Gasdermin E-derived caspase-3 inhibitors effectively protect mice from acute hepatic failure
Acta Pharmacologica Sinica (2021)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
