Mechanism of action of Drosophila Reaper in mammalian cells: Reaper globally inhibits protein synthesis and induces apoptosis independent of mitochondrial permeability

Tait, S.W.G. , Werner, A.B., de Vries, E. and Borst, J. (2004) Mechanism of action of Drosophila Reaper in mammalian cells: Reaper globally inhibits protein synthesis and induces apoptosis independent of mitochondrial permeability. Cell Death and Differentiation, 11(8), pp. 800-811. (doi:10.1038/sj.cdd.4401410)

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Publisher's URL: http://dx.doi.org/10.1038/sj.cdd.4401410

Abstract

Drosophila Reaper can bind inhibitor of apoptosis proteins (IAP) and thereby rescue caspases from proteasomal degradation. In insect cells, this is sufficient to induce apoptosis. Reaper can also induce apoptosis in mammalian cells, in which caspases need to be activated, usually via the mitochondrial pathway. Nevertheless, we find that Reaper efficiently induces apoptosis in mammalian cells in the absence of mitochondrial permeabilisation and cytochrome c release. Moreover, this capacity was only marginally affected by deletion of Reaper's amino-terminal IAP-binding motif. Independent of this motif, Reaper could globally suppress protein synthesis. Deletion of 20 amino acids from the carboxy-terminus of Reaper fully abrogated its potential to inhibit protein synthesis and to induce apoptosis in the absence of IAP-binding. Our findings indicate that the newly identified capacity of Reaper to suppress protein translation can operate in mammalian cells and may be key to its pro-apoptotic activity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tait, Professor Stephen
Authors: Tait, S.W.G., Werner, A.B., de Vries, E., and Borst, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell Death and Differentiation
ISSN:1350-9047
ISSN (Online):1476-5403
Published Online:26 March 2004

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