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Oncogenic Ras-mediated downregulation of Gadd153/CHOP is required for Ras-induced cellular transformation

Rong Rong1, JoAnne Montalbano, Weixin Jin

  • 1Department of Pharmacology, State University of New York, Upstate Medical University, 750 E Adams Street, Syracuse, NY 13210, USA.

Oncogene
|May 5, 2005
PubMed

Insights

Oncogenic Ras proteins reduce the expression of Gadd153 (growth inhibitory protein), impacting cell growth and survival. This downregulation is crucial for Ras-driven cellular transformation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Oncogenic Ras proteins drive cell proliferation and survival through downstream signaling.
  • Gadd153 (CHOP) is a proapoptotic protein upregulated by apoptotic stimuli.

Purpose of the Study:

  • To investigate the effect of oncogenic Ras on Gadd153 expression.
  • To determine the mechanism of Gadd153 downregulation by oncogenic Ras.
  • To assess the role of Gadd153 in Ras-mediated cellular transformation.

Main Methods:

  • Western blotting and quantitative PCR to measure Gadd153 protein and mRNA levels.
  • mRNA stability assays to assess GADD153 mRNA decay rates.
  • Transfection experiments to evaluate the effect of exogenous Gadd153 on Ras transformation.

Main Results:

  • Oncogenic Ras downregulates Gadd153 at both protein and mRNA levels.
  • Gadd153 downregulation is mediated, in part, by decreased mRNA stability.
  • Downregulation is specific to oncogenic Ras, not R-Ras2/TC21.
  • Exogenous Gadd153 expression inhibits Ras-induced oncogenic transformation.

Conclusions:

  • Oncogenic Ras actively downregulates Gadd153 expression.
  • Gadd153 downregulation is a key mechanism promoting Ras-driven cellular transformation.
  • Modulation of growth-inhibitory molecules like Gadd153 is integral to oncogenic transformation.

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