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Heat shock factor 1-mediated thermotolerance prevents cell death and results in G2/M cell cycle arrest. Cell Stress Chaperones 2001 Oct;6(4):326-36



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Scopus ID

2-s2.0-0035204193   41 Citations


Mammalian cells respond to environmental stress by activating heat shock transcription factors (eg, Hsf1) that regulate increased synthesis of heat shock proteins (Hsps). Hsps prevent the disruption of normal cellular mitosis, meiosis, or differentiation by environmental stressors. To further characterize this stress response, transformed wild-type Hsf1+/+ and mutant Hsf1-/- mouse embryonic fibroblasts (MEFs) were exposed to (1) lethal heat (45 degrees C, 60 minutes), (2) conditioning heat (43 degrees C, 30 minutes), or (3) conditioning followed by lethal heat. Western blot analysis demonstrated that only Hsf1+/+ MEFs expressed inducible Hsp70s and Hsp25 following conditioning or conditioning and lethal heat. Exposure of either Hsf1+/+ or Hsf1-/- MEFs to lethal heat resulted in cell death. However, if conditioning heat was applied 6 hours before lethal heat, more than 85% of Hsf1+/+ MEFs survived, and cells in G2/M transiently increased 3-fold. In contrast, conditioned Hsf1-/- MEFs neither survived lethal heat nor exhibited this G2/M accumulation. Coinfection with adenoviral Hsp70 and Hsp25 constructs did not fully recreate thermotolerance in either Hsf1+/+ or Hsf1-/- MEFs, indicating other Hsf1-mediated gene expression is required for complete thermotolerance. These results demonstrate the necessity of Hsf1-mediated gene expression for thermotolerance and the involvement of cell cycle regulation, particularly the G2/M transition, in this thermotolerant response.

Author List

Luft JC, Benjamin IJ, Mestril R, Dix DJ


Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Death
Cell Line, Transformed
Cell Survival
DNA-Binding Proteins
G2 Phase
Heat Shock Transcription Factors
Heat-Shock Proteins
Heat-Shock Response
Hot Temperature
Time Factors
Transcription Factors
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a