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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

Aberrant expression of c-Jun in glioblastoma by internal ribosome entry site (IRES)-mediated translational activation

Lior Blau1, Revital Knirsh, Iris Ben-Dror

  • 1Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.

Proceedings of the National Academy of Sciences of the United States of America
|October 3, 2012
PubMed

Insights

Elevated c-Jun protein in glioblastoma stems from enhanced translation, not increased mRNA. This discovery reveals a new cancer mechanism involving an internal ribosomal entry site (IRES) in c-Jun, offering novel therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The protooncogene c-Jun is crucial for cell growth and cancer development.
  • Aberrant c-Jun expression is linked to various human cancers, but the regulatory mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the mechanisms behind elevated c-Jun protein accumulation in human glioblastoma.
  • To explore the role of translational control in c-Jun-mediated oncogenesis.

Main Methods:

  • Analysis of c-Jun mRNA and protein levels in glioblastoma samples.
  • Investigation of the 5' untranslated region (5'UTR) of c-Jun for regulatory elements.
  • Assessment of cap-independent translation mechanisms.
  • Examination of pathways regulating c-Jun accumulation, including MAPK and cytoskeleton-dependent pathways.

Main Results:

  • c-Jun protein accumulation is significantly elevated in human glioblastoma without corresponding increases in mRNA or protein half-life.
  • A potent internal ribosomal entry site (IRES) within the c-Jun 5'UTR drives cap-independent translation in glioblastoma cells.
  • c-Jun accumulation is regulated by a cytoskeleton-dependent pathway, independent of MAPK activity.

Conclusions:

  • Human c-Jun utilizes an IRES-mediated translational activation mechanism contributing to glioblastoma development.
  • This novel mechanism of c-Jun regulation via translational control offers potential therapeutic targets for glioblastoma and possibly other cancers.

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