Epigenetic activation of a subset of mRNAs by eIF4E explains its effects on cell proliferation

Yaël Mamane1, Emmanuel Petroulakis, Yvan Martineau

  • 1Department of Biochemistry, McGill Cancer Centre, McGill University, Montreal, Quebec, Canada.

Plos One
|February 22, 2007
PubMed
Abstract

Insights

Increased expression of eukaryotic initiation factor 4E (eIF4E) enhances cell growth and survival by upregulating specific mRNAs, including those involved in anti-apoptosis. Targeting eIF4E offers a potential cancer therapy strategy.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Deregulation of mRNA translation drives aberrant cell growth, proliferation, and survival.
  • Eukaryotic initiation factor 4E (eIF4E), the mRNA 5' cap-binding protein, is a key regulator of translational control.
  • Understanding eIF4E's role in cell proliferation and survival requires identifying its translationally responsive mRNA targets.

Purpose of the Study:

  • To investigate how eIF4E influences cell proliferation and survival.
  • To identify novel mRNA targets translationally regulated by eIF4E.
  • To elucidate the mechanisms by which eIF4E promotes cell survival and transformation.

Main Methods:

  • Utilized microarray analysis of polysomal mRNA from an eIF4E-inducible NIH 3T3 cell line.
  • Quantified changes in mRNA translation upon inducible eIF4E expression.
  • Identified specific mRNA sets translationally modulated by eIF4E.

Main Results:

  • Inducible eIF4E expression led to increased translation of specific mRNA sets.
  • Identified novel eIF4E targets, including mRNAs for ribosomal proteins and cell growth factors.
  • Observed augmented translation of anti-apoptotic mRNAs, conferring resistance to endoplasmic reticulum-mediated apoptosis.

Conclusions:

  • eIF4E plays a critical role in preventing apoptosis and promoting cell transformation.
  • The findings provide new insights into eIF4E-mediated mechanisms of cell survival.
  • Downregulation of eIF4E and its targets represents a potential therapeutic strategy for anti-cancer drug development.

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