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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
10:00

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

PML RING suppresses oncogenic transformation by reducing the affinity of eIF4E for mRNA

N Cohen1, M Sharma, A Kentsis

  • 1Structural Biology Program, Department of Physiology & Biophysics, Mount Sinai School of Medicine, New York University, One Gustave Levy Place, New York, NY 10029, USA.

The EMBO Journal
|August 14, 2001
PubMed

Insights

The promyelocytic leukemia protein (PML) binds eukaryotic initiation factor 4E (eIF4E), reducing its activity. This interaction inhibits oncogenic transformation by decreasing Cyclin D1 levels, revealing PML

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • The promyelocytic leukemia protein (PML) forms nuclear bodies crucial for suppressing oncogenic transformation and growth.
  • The precise biochemical functions of PML bodies remain largely unknown, despite their association with human diseases.

Purpose of the Study:

  • To elucidate the biochemical mechanisms underlying the transformation-suppressive activity of PML.
  • To investigate the interaction between PML and eukaryotic initiation factor 4E (eIF4E).

Main Methods:

  • Demonstrated direct binding between the PML RING domain and eIF4E.
  • Assessed the effect of PML on eIF4E's affinity for the 5' m(7)G cap of mRNA.
  • Analyzed the impact of PML-eIF4E interaction on Cyclin D1 mRNA transport and protein levels.

Main Results:

  • PML directly binds to the PML RING domain, which is essential for PML body association and transformation suppression.
  • PML binding significantly reduces eIF4E's affinity for the mRNA cap, thereby inhibiting Cyclin D1 mRNA transport and translation.
  • This modulation of eIF4E activity by PML leads to decreased Cyclin D1 protein levels and consequent inhibition of transformation.

Conclusions:

  • PML directly modulates the function of nuclear eIF4E, establishing a novel mechanism for transformation suppression.
  • This study provides the first biochemical framework for understanding how PML inhibits oncogenic transformation.

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