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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
PubMed

Insights

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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