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Regulation of c-myc expression by IFN-gamma through Stat1-dependent and -independent pathways

C V Ramana1, N Grammatikakis, M Chernov

  • 1Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

The EMBO Journal
|January 19, 2000
PubMed

Insights

Interferons (IFNs) normally suppress cell growth by regulating c-myc expression via Stat1. However, Stat1-null cells show increased c-myc, revealing a novel pathway involving PKR and Raf-1.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Interferons (IFNs) regulate cell growth through Stat1-dependent pathways.
  • c-myc expression is a key target for IFN-mediated growth inhibition.

Purpose of the Study:

  • To elucidate the role of Stat1 in IFN-gamma-induced c-myc regulation.
  • To identify novel signaling pathways involved in IFN response.

Main Methods:

  • Utilized wild-type and Stat1-null mouse embryo fibroblasts.
  • Investigated c-myc mRNA expression and Stat1 phosphorylation.
  • Employed PKR-null cells and inhibitors of HSP90-Raf-1 interaction.

Main Results:

  • IFN-gamma suppresses c-myc in wild-type cells but induces it in Stat1-null cells.
  • Stat1 phosphorylation (tyrosine and serine) is crucial for suppression.
  • PKR and Raf-1 are implicated in a Stat1-independent pathway for c-myc induction.

Conclusions:

  • Stat1 is essential for IFN-gamma-mediated suppression of c-myc.
  • A novel Stat1-independent pathway involving PKR and Raf-1 promotes c-myc induction in response to IFN-gamma.
  • Understanding these pathways is critical for cell growth regulation.

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