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

Caoimhín G Concannon, Una FitzGerald, Carina I Holmberg, Eva Szegezdi, Lea Sistonen, Afshin Samali

Research output: Contribution to journalArticleScientificpeer-review


Engagement of death receptors induces caspase activation and apoptosis. A recent study reported altered protein expression, including increased Hsp70 levels during CD95-mediated apoptosis. Here, we examined the mechanism underlying increased Hsp70 levels in cells challenged with a monoclonal antibody directed against the CD95 receptor. Levels of Hsp70 were found to increase in a dose-dependent manner, occurring independently of either heat shock factor 1 activation or the accumulation of Hsp70 messenger ribonucleic acid (mRNA), suggesting the involvement of posttranslational modifications. Inhibition of translation and de novo protein synthesis by cycloheximide resulted in Hsp70 protein levels diminishing over time in control cells, whereas its level remained constant during CD95 signaling. In addition, death receptor activation through exposure of cells to tumor necrosis factor-related apoptosis-inducing ligand did not alter Hsp70 levels. These findings demonstrate that receptor-specific signaling through the CD95 increases the stability of Hsp70 protein, rather than mRNA, when compared with control cells. The results describe a novel mechanism of heat shock protein accumulation, where increased protein stability and reduced turnover, is the mechanism by which Hsp70 accumulates in cells during CD95-mediated apoptosis.

Original languageEnglish
Pages (from-to)59-65
Number of pages7
JournalCell Stress and Chaperones
Issue number1
Publication statusPublished - 2005
MoE publication typeA1 Journal article-refereed


  • Apoptosis
  • Blotting, Western
  • Caspases/metabolism
  • Cycloheximide/pharmacology
  • Dose-Response Relationship, Drug
  • Electrophoretic Mobility Shift Assay
  • Enzyme Activation
  • Flow Cytometry
  • HSP70 Heat-Shock Proteins/metabolism
  • Humans
  • Jurkat Cells
  • Protein Processing, Post-Translational
  • Protein Synthesis Inhibitors/pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • fas Receptor/metabolism


Dive into the research topics of 'CD95-mediated alteration in Hsp70 levels is dependent on protein stabilization'. Together they form a unique fingerprint.

Cite this