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Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB
A Kauffmann-Zeh1, P Rodriguez-Viciana, E Ulrich
1Imperial Cancer Research Fund, London, UK.
Nature
|February 6, 1997
Summary
Ras signaling activates contradictory pathways, suppressing c-Myc-induced apoptosis via Phosphatidylinositol-3-kinase (PI(3)K) and protein kinase B/Akt, but promoting apoptosis through the Raf pathway.
Area of Science:
- Cellular biology
- Molecular oncology
- Signal transduction
Background:
- Cell viability relies on survival factors that inhibit apoptosis, a programmed cell death process.
- Defects in anti-apoptotic pathways are linked to pathologies like cancer, where tumor cells must evade apoptosis.
- Phosphatidylinositol-3-kinase (PI(3)K) is crucial for intracellular signal transduction and survival signaling.
Purpose of the Study:
- To investigate the roles of PI(3)K, Ras, PKB/Akt, and p70S6K in modulating apoptosis induced by the oncoprotein c-Myc.
- To elucidate the dual role of Ras in regulating cell viability through distinct signaling pathways.
Main Methods:
- Fibroblast apoptosis induction by c-Myc.
- Analysis of Ras, PI(3)K, PKB/Akt, and p70S6K signaling pathways.
- Assessment of cell viability and apoptosis modulation.
Main Results:
- Ras activation of PI(3)K suppresses c-Myc-induced apoptosis by activating PKB/Akt, but not p70S6K.
- Ras also promotes apoptosis via the Raf pathway, indicating contradictory signaling.
- Ras activation of PI(3)K and PKB/Akt is essential for suppressing c-Myc-induced apoptosis.
Conclusions:
- Ras exhibits a dual role in cell viability, capable of both suppressing and promoting apoptosis.
- The PI(3)K/PKB/Akt pathway is a key mediator of Ras-dependent suppression of c-Myc-induced apoptosis.
- Ras-induced apoptosis may limit the proliferation of somatic cells with oncogenic Ras mutations.
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