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Caspase 2-mediated tumor suppression involves survivin gene silencing

Oncogene volume 29, pages 1280–1292 (2010)Cite this article

Abstract

One of the pivotal functions of endogenous tumor suppression is to oppose aberrant cell survival, but the molecular requirements of this process are not completely understood. Here, we show that caspase 2, a death effector with largely unknown functions, represses transcription of the survivin gene, a general regulator of cell division and cytoprotection in tumors. This pathway involves caspase 2 proteolytic cleavage of the nuclear factor κB (NFκB) activator, RIP1. In turn, loss of RIP1 abolishes transcription of NFκB target genes, including survivin, resulting in deregulated mitotic transitions, enhanced apoptosis and suppression of tumorigenicity in vivo. Therefore, caspase 2 functions as an endogenous inhibitor of NFκB-dependent cell survival and this mechanism may contribute to tumor suppression in humans.

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Acknowledgements

We thank Drs Bert Vogelstein, Michelle Kelliher and Neal Silverman for reagents. This work was supported by the National Institutes of Health grants CA78810, CA90917 and CA118005.

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  1. Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA

    M Guha, F Xia, C M Raskett & D C Altieri

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Correspondence to D C Altieri.

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Guha, M., Xia, F., Raskett, C. et al. Caspase 2-mediated tumor suppression involves survivin gene silencing. Oncogene 29, 1280–1292 (2010). https://doi.org/10.1038/onc.2009.428

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