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Signalling to eIF4E in cancer.

Nadeem Siddiqui1, Nahum Sonenberg2

  • 1Department of Biochemistry and Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montreal, Quebec, Canada H3A 1A3.

Biochemical Society Transactions
|October 31, 2015
PubMed
Summary
This summary is machine-generated.

Translational control, regulated by eukaryotic translation initiation factor 4E (eIF4E), is crucial for gene expression and cellular processes. Its dysregulation in cancer highlights its potential as a therapeutic target.

Keywords:
cancer therapyeukaryotic translation initiation factor 4E (eIF4E)eukaryotic translation initiation factor 4E-binding proteins (4E-BPs)mechanistic/mammalian target of rapamycin (mTOR)mitogen-activated protein kinase-interacting kinase 1/2 (Mnk1/2)phospho-4E

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Translational control is vital for eukaryotic gene expression, impacting proliferation, apoptosis, and differentiation.
  • It primarily occurs during initiation, involving ribosome recruitment to mRNA.
  • Eukaryotic translation initiation factor 4E (eIF4E) is central to this process, binding mRNA and aiding ribosomal subunit recruitment.

Purpose of the Study:

  • To elucidate the role of translational control via eIF4E in cancer.
  • To explore the signaling pathways regulating eIF4E activity in tumorigenesis.
  • To identify eIF4E and its associated pathways as potential therapeutic targets in cancer therapy.

Main Methods:

  • Analysis of signaling pathways including PI3K/Akt/mTOR and Ras/MAPK/Mnk.
  • Investigation of eIF4E phosphorylation and its binding to 4E-BPs.
  • Examination of eIF4E activity in cancer cells.

Main Results:

  • The PI3K/Akt/mTOR and Ras/MAPK/Mnk pathways profoundly regulate eIF4E activity.
  • mTOR phosphorylates 4E-BPs, relieving translational suppression, while Mnk phosphorylates eIF4E, stimulating translation.
  • Hyperactivation of these pathways in cancer leads to increased eIF4E activity, promoting tumorigenesis.

Conclusions:

  • Translational control mediated by eIF4E is a convergence point for oncogenic signaling pathways.
  • Targeting eIF4E regulatory pathways offers a promising strategy for cancer therapy.