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R-Ras promotes apoptosis caused by growth factor deprivation via a Bcl-2 suppressible mechanism

H G Wang1, J A Millan, A D Cox

  • 1La Jolla Cancer Research Foundation, California 92037, USA.

The Journal of Cell Biology
|May 1, 1995
PubMed

Insights

Ras-related C3 botulinum toxin substrate 1 (R-Ras) protein promotes apoptosis in growth factor-deprived cells. Bcl-2 protein counteracts R-Ras-induced cell death, acting downstream of R-Ras signaling to promote survival.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Apoptosis Regulation

Background:

  • Bcl-2 protein is a key regulator of programmed cell death (apoptosis).
  • The precise biochemical mechanism of Bcl-2's anti-apoptotic function is not fully understood.
  • Bcl-2 has been reported to interact with Ras-related C3 botulinum toxin substrate 1 (R-Ras), a small GTPase.

Purpose of the Study:

  • To investigate the functional role of R-Ras in regulating cell death pathways.
  • To elucidate the relationship between R-Ras activity and Bcl-2's anti-apoptotic function.

Main Methods:

  • Stable transfection of IL-3-dependent cell lines (32D.3, FL5.12) with activated R-Ras (R-Ras(38V)).
  • Co-transfection experiments with R-Ras(38V) and Bcl-2 expression plasmids.
  • Assessment of cell death rates upon growth factor deprivation.
  • Analysis of R-Ras GDP/GTP binding and Raf-1 kinase activation.

Main Results:

  • Cells expressing activated R-Ras showed increased apoptotic cell death when deprived of IL-3.
  • Higher R-Ras protein levels correlated with faster cell death rates.
  • Bcl-2 expression abrogated R-Ras-induced cell death in both IL-3-deprived and serum-deprived cells.
  • Bcl-2 did not alter R-Ras GDP/GTP regulation or R-Ras-mediated Raf-1 activation.

Conclusions:

  • R-Ras enhances the activity of a cell death pathway in growth factor-deprived cells.
  • Bcl-2 acts downstream of R-Ras to promote cell survival, counteracting R-Ras-induced apoptosis.
  • Bcl-2's anti-apoptotic effect is independent of R-Ras GTPase activity or Raf-1 activation.

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