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Rockefeller University Press, Journal of Cell Biology, 3(152), p. 483-490, 2001

DOI: 10.1083/jcb.152.3.483

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Diablo Promotes Apoptosis by Removing Miha/Xiap from Processed Caspase 9

Journal article published in 2001 by Paul G. Ekert ORCID, John Hendry Silke ORCID, Christine J.-O.-Y. Hawkins, Anne M. Verhagen, David L. Vaux
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

MIHA is an inhibitor of apoptosis protein (IAP) that can inhibit cell death by direct interaction with caspases, the effector proteases of apoptosis. DIABLO is a mammalian protein that can bind to IAPs and antagonize their antiapoptotic effect, a function analogous to that of the proapoptotic Drosophila molecules, Grim, Reaper, and HID. Here, we show that after UV radiation, MIHA prevented apoptosis by inhibiting caspase 9 and caspase 3 activation. Unlike Bcl-2, MIHA functioned after release of cytochrome c and DIABLO from the mitochondria and was able to bind to both processed caspase 9 and processed caspase 3 to prevent feedback activation of their zymogen forms. Once released into the cytosol, DIABLO bound to MIHA and disrupted its association with processed caspase 9, thereby allowing caspase 9 to activate caspase 3, resulting in apoptosis.