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X-linked IAP is a direct inhibitor of cell-death proteases

Nature volume 388, pages 300–304 (1997)Cite this article

Abstract

The inhibitor-of-apoptosis (IAP) family of genes has an evolutionarily conserved role in regulating programmed cell death in animals ranging from insects to humans1,2,3,4,5,6. Ectopic expression of human IAP proteins can suppress cell death induced by a variety of stimuli, but the mechanism of this inhibition was previously unknown. Here we show that human X-chromosome-linked IAP directly inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. As the caspases are highly conserved throughout the animal kingdom and are the principal effectors of apoptosis7, our findings suggest how IAPs might inhibit cell death, providing evidence for a mechanism of action for these mammalian cell-death suppressors.

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Figure 1: XIAP inhibits cytochrome-c-induced processing of caspase-3 and destruction of nuclei in cytosolic extracts.
Figure 2: XIAP directly binds and inhibits caspase-3 and caspase-7.
Figure 3: XIAP inhibits Bax-induced caspase-3 processing and cell death in 293T cells.

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Author notes

  1. Quinn L. Deveraux and Ryosuke Takahashi: These authors contributed equally to this work.

Authors and Affiliations

  1. The Burnham Institute, Program on Apoptosis and Cell Death Research, 10901 North Torrey Pines Road, La Jolla, 92037, California, USA

    Guy S. Salvesen & John C. Reed

Authors
  1. Quinn L. Deveraux
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  2. Ryosuke Takahashi
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  3. Guy S. Salvesen
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  4. John C. Reed
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Correspondence to John C. Reed.

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Deveraux, Q., Takahashi, R., Salvesen, G. et al. X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388, 300–304 (1997). https://doi.org/10.1038/40901

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