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Published on: January 22, 2019

Ribosomal protein S6 is a selective mediator of TRAIL-apoptotic signaling

Y-J Jeon1, I K Kim, S-H Hong

  • 1School of Biological Science/Bio-Max Institute, Seoul National University, Seoul, Korea.

Oncogene
|March 26, 2008
PubMed

Insights

Ribosomal protein S6 (rpS6) selectively mediates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Reduced rpS6 sensitizes cells to TRAIL, highlighting its therapeutic potential in cancer treatment.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells, showing therapeutic promise.
  • Understanding TRAIL-induced death signaling is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To identify genetic factors mediating TRAIL-induced apoptosis.
  • To elucidate the role of ribosomal protein S6 (rpS6) in TRAIL signaling.

Main Methods:

  • Functional genetic screening to identify TRAIL-resistant clones.
  • rpS6 knockdown and ectopic expression studies in Jurkat, HeLa, and MEF cells.
  • Analysis of apoptosis induction by various death ligands and chemotherapeutic agents.

Main Results:

  • Reduced rpS6 expression attenuated TRAIL-induced apoptosis but not apoptosis induced by other death signals.
  • rpS6 knockdown downregulated Death Receptor 4 (DR4).
  • Unphosphorylated rpS6 enhanced TRAIL sensitivity, suggesting its critical role in mediating TRAIL-induced cell death.

Conclusions:

  • Ribosomal protein S6 (rpS6) acts as a selective mediator of TRAIL-induced apoptosis.
  • The unphosphorylated form of rpS6 is particularly important for TRAIL sensitivity.
  • Targeting rpS6 phosphorylation may offer a novel strategy for enhancing TRAIL-based cancer therapy.

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