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Ras mediates cell survival by regulating tuberin

Oncogene volume 27, pages 2072–2083 (2008)Cite this article

Abstract

Mutational activation of Ras promotes oncogenesis by controlling cell cycle regulation and cell survival. Ras-mediated activation of both, the PI3K/AKT pathway and the MEK/ERK pathway, can trigger downregulation of the function of tuberin to block the activities of mTOR and p70S6K. Here we demonstrate that Ras-induced cell survival is accompanied by upregulation of p70S6K activity. Ras harbors the potential to negatively affect tuberin-induced apoptosis and p70S6K inactivation. These effects of Ras were found to depend on its potential to regulate the MEK/ERK pathway. Experiments using tuberin-negative fibroblasts revealed that the potential of Ras to counteract apoptosis depends on functional tuberin. Taken together, we provide evidence that the function of Ras to trigger inactivation of tuberin plays a major role in the regulation of cell survival upon mutational activation of the oncogene Ras. This is the first description of a functional interaction between the tumor suppressor tuberin and the oncogene Ras in regulating apoptosis.

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Acknowledgements

The authors wish to thank Drs AJ Beavis, J Blenis, B Manning, T Ströbel, R Yeung for reagents. This research has been supported by the Herzfelder'sche Familienstiftung (Vienna, Austria) by the RedBull company (Salzburg, Austria) and by the FWF Austrian Science Fund (P18894-B12).

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  1. Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria

    A Freilinger, M Rosner, M Hanneder & M Hengstschläger

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  1. A Freilinger
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  2. M Rosner
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Correspondence to M Hengstschläger.

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Freilinger, A., Rosner, M., Hanneder, M. et al. Ras mediates cell survival by regulating tuberin. Oncogene 27, 2072–2083 (2008). https://doi.org/10.1038/sj.onc.1210844

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