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Updated: Aug 18, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

Regulation of the phosphorylation and integrity of protein synthesis initiation factor eIF4GI and the translational

Constantina Constantinou1, Michael J Clemens

  • 1Translational Control Group, Department of Basic Medical Sciences (Biochemistry and Immunology), St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.

Oncogene
|May 18, 2005
PubMed

Insights

Activation of mouse p53 rapidly inhibits protein synthesis by modifying initiation factors eIF4GI and 4E-BP1. This caspase-independent process affects eIF4F complex formation, distinct from mTOR signaling.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Protein synthesis is crucial for cell function and tightly regulated.
  • The p53 tumor suppressor protein plays diverse roles beyond cell cycle arrest.
  • Initiation factors like eIF4GI and 4E-BP1 are key regulators of cap-dependent translation.

Purpose of the Study:

  • To investigate the mechanism by which p53 activation inhibits protein synthesis.
  • To elucidate the role of p53 in regulating translation initiation factors eIF4GI and 4E-BP1.
  • To compare the effects of p53 activation with mTOR inhibition on protein synthesis.

Main Methods:

  • Activation of a temperature-sensitive p53 in murine erythroleukaemia cells.
  • Analysis of protein synthesis rates.
  • Western blotting to assess phosphorylation and cleavage of eIF4GI and 4E-BP1.
  • Co-immunoprecipitation to study protein-protein interactions.
  • Treatment with mTOR inhibitor rapamycin for comparison.

Main Results:

  • p53 activation rapidly inhibited protein synthesis.
  • Dephosphorylation and cleavage of eIF4GI and 4E-BP1 were observed.
  • Cleavage of 4E-BP1 was caspase-independent.
  • p53 effects on these factors were distinct but additive to rapamycin.
  • p53 inhibited a rapamycin-insensitive kinase activity against 4E-BP1.

Conclusions:

  • p53 activation inhibits protein synthesis initiation through modification of eIF4GI and 4E-BP1.
  • The mechanism is largely independent of the mTOR pathway.
  • Caspase-independent cleavage of 4E-BP1 contributes to translation regulation by p53.

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