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CD95-mediated alteration in Hsp70 levels is dependent on protein stabilization

Caoimhín G Concannon1, Una FitzGerald, Carina I Holmberg

  • 1Cell Stress and Apoptosis Research Group, Department of Biochemistry and National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.

Cell Stress & Chaperones
|April 19, 2005
PubMed

Insights

CD95 signaling increases heat shock protein 70 (Hsp70) levels by enhancing protein stability, not mRNA accumulation. This novel mechanism involves reduced Hsp70 turnover during CD95-mediated apoptosis.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Immunology

Background:

  • Engagement of death receptors triggers caspase activation and apoptosis.
  • Previous studies indicated elevated heat shock protein 70 (Hsp70) levels during CD95-mediated apoptosis.

Purpose of the Study:

  • To investigate the mechanism behind increased Hsp70 levels during CD95 receptor-mediated apoptosis.
  • To determine if Hsp70 accumulation is regulated at the mRNA or posttranslational level.

Main Methods:

  • Challenging cells with a monoclonal antibody against the CD95 receptor.
  • Assessing Hsp70 levels, heat shock factor 1 activation, and Hsp70 mRNA accumulation.
  • Utilizing cycloheximide to inhibit protein synthesis and evaluating Hsp70 stability.
  • Comparing CD95 signaling with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment.

Main Results:

  • Hsp70 levels increased in a dose-dependent manner upon CD95 receptor engagement.
  • Hsp70 accumulation occurred independently of heat shock factor 1 activation or increased Hsp70 mRNA levels.
  • CD95 signaling maintained Hsp70 protein levels despite inhibited de novo protein synthesis, unlike control cells.
  • TRAIL-induced apoptosis did not affect Hsp70 levels, indicating receptor-specific effects.

Conclusions:

  • CD95 receptor signaling enhances Hsp70 protein stability, leading to its accumulation.
  • This mechanism involves increased protein stability and reduced turnover, a novel pathway for heat shock protein accumulation during apoptosis.
  • The findings highlight a posttranslational regulation of Hsp70 during CD95-mediated cell death.

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