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Updated: Dec 18, 2025

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

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Selective Translation of Cell Fate Regulators Mediates Tolerance to Broad Oncogenic Stress

Elise Y Cai1, Megan N Kufeld2, Samantha Schuster3

  • 1Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA; Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98195, USA.

Cell Stem Cell
|June 10, 2020
PubMed

Insights

Human skin can tolerate many oncogenic lesions. A new study reveals a translational mechanism involving eIF2B5 that coordinates HRAS-driven proliferation with progenitor cell loss, preventing tumor growth.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Dermatology

Background:

  • Human skin exhibits remarkable tolerance to oncogenic lesions.
  • Mechanisms controlling tolerance to widespread oncogene activation in tissues remain largely unknown.

Purpose of the Study:

  • To investigate the translational mechanisms coordinating oncogene-induced proliferation and progenitor cell fate in skin.
  • To identify key regulators of oncogene tolerance and tumorigenesis.

Main Methods:

  • In vivo ribosome profiling to analyze translation dynamics.
  • Genetic screening to identify regulatory genes.
  • Analysis of HRAS oncogene activation in epidermal tissue.

Main Results:

  • Oncogenic HRAS triggers hyperproliferation coupled with loss of progenitor self-renewal via a translational mechanism.
  • Translation initiator eIF2B5 is identified as a key regulator of HRAS-driven proliferation and cell fate.
  • FBXO32, a ubiquitin ligase, restrains epidermal renewal, thereby limiting HRAS-driven tumorigenesis while preserving normal tissue growth.

Conclusions:

  • Translational control plays a critical role in managing oncogenic stress in tissues.
  • eIF2B5-mediated translation of ubiquitination genes directs progenitor cell fate to prevent widespread tumorigenesis.
  • Oncogene-driven translation can be a protective mechanism, steering cell fate to maintain normal tissue function under stress.
Keywords:
epidermisfate coordinationhomeostasisoncogenic stressoncogenic tolerancestem cell renewaltranslational regulationtumor suppression

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