Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB

Andrea Kauffmann-Zeh, Pablo Rodriguez-Viciana, Eugen Ulrich, Christopher Gilbert, Paul Coffer, Julian Downward and Gerard Evan
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Andrea Kauffmann-Zeh: Imperial Cancer Research Fund
Pablo Rodriguez-Viciana: Imperial Cancer Research Fund
Eugen Ulrich: Imperial Cancer Research Fund
Christopher Gilbert: Imperial Cancer Research Fund
Paul Coffer: University Hospital Utrecht
Julian Downward: Imperial Cancer Research Fund
Gerard Evan: Imperial Cancer Research Fund

Nature, 1997, vol. 385, issue 6616, 544-548

Abstract: Abstract The viability of vertebrate cells depends on survival factors which activate signal transduction pathways that suppress apoptosis. Defects in anti-apoptotic signalling pathways are implicated in many pathologies including cancer, in which apoptosis induced by deregulated oncogenes must be forestalled for a tumour to become established. Phosphatidylinositol-3-kinase (PI(3)K) is involved in the intracellular signal transduction of many receptors and has been implicated in the transduction of survival signals in neuronal cells1. We therefore examined the role of PI(3)K, its upstream effector Ras2, and its putative downstream protein kinase effectors PKB/Akt3,4 and p70S6K (ref. 5) in the modulation of apoptosis induced in fibroblasts by the oncoprotein c-Myc. Here we show that Ras activation of PI(3)K suppresses c-Myc-induced apoptosis through the activation of PKB/Akt but not p70S6K. However, we also found that Ras is an effective promoter of apoptosis, through the Raf pathway. Thus Ras activates contradictory intracellular pathways that modulate cell viability. Induction of apoptosis by Ras may be an important factor in limiting the expansion of somatic cells that sustain oncogenic ras mutations.cells

Date: 1997
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DOI: 10.1038/385544a0

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