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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
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.
Background:
Translation deregulation is an important mechanism that causes aberrant cell growth, proliferation and survival. eIF4E, the mRNA 5' cap-binding protein, plays a major role in translational control. To understand how eIF4E affects cell proliferation and survival, we studied mRNA targets that are translationally responsive to eIF4E.
Methodology/Principal Findings:
Microarray analysis of polysomal mRNA from an eIF4E-inducible NIH 3T3 cell line was performed. Inducible expression of eIF4E resulted in increased translation of defined sets of mRNAs. Many of the mRNAs are novel targets, including those that encode large- and small-subunit ribosomal proteins and cell growth-related factors. In addition, there was augmented translation of mRNAs encoding anti-apoptotic proteins, which conferred resistance to endoplasmic reticulum-mediated apoptosis.
Conclusions/Significance:
Our results shed new light on the mechanisms by which eIF4E prevents apoptosis and transforms cells. Downregulation of eIF4E and its downstream targets is a potential therapeutic option for the development of novel anti-cancer drugs.
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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