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Regulation of mitochondrial Smac/DIABLO-selective release by survivin

Oncogene volume 26, pages 7569–7575 (2007)Cite this article

Abstract

The intrinsic apoptotic pathway is characterized by the release of several mitochondrial intermembrane proteins into the cytosol of dying cells. It is unclear whether the release of these proteins follows a common or specific pathway. In the present report we show that survivin and, to a lesser extent, the survivin splice variant survivin DeltaEx3 regulate the specific liberation of second mitochondria-derived activator of caspase/direct IAP binding protein with low pI (Smac/DIABLO), an inhibitor of apoptosis proteins binding protein, during apoptosis induced by etoposide, a DNA damaging agent. This antineoplastic drug induced posttranscriptional upregulation of survivin and survivin DeltaEx3. In turn, mitochondrial survivin associated with Smac/DIABLO, delaying its release. In addition, cytosolic survivin also stabilized the cytosolic levels of released Smac/DIABLO. These results provide an explanation for the observed differences in the release of mitochondrial intermembrane proteins in various apoptotic models and present a new mechanism for the anti-apoptotic effects of survivin in cancer cells.

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Acknowledgements

We thank Dr Stanley Korsmeyer for the kind gift of the BK-KS-Bcl-2 plasmid. This work was supported by grant C01-45728 from CONACyT to J Melendez-Zajgla. G Ceballos-Cancino was supported by a fellowship from CONACyT. The present work was part of G Ceballos-Cancino doctoral thesis from the UNAM (Biomedical Doctorate Program, Faculty of Medicine).

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  1. Molecular Biology Laboratory, Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Tlalpan, Mexico City, Mexico

    G Ceballos-Cancino, M Espinosa, V Maldonado & J Melendez-Zajgla

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  1. G Ceballos-Cancino
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  2. M Espinosa
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  3. V Maldonado
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  4. J Melendez-Zajgla
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Correspondence to V Maldonado or J Melendez-Zajgla.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Ceballos-Cancino, G., Espinosa, M., Maldonado, V. et al. Regulation of mitochondrial Smac/DIABLO-selective release by survivin. Oncogene 26, 7569–7575 (2007). https://doi.org/10.1038/sj.onc.1210560

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