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HEAT SHOCK FACTOR 1-MEDIATED THERMOTOLERANCE PREVENTS CELL DEATH AND RESULTS IN G2/M CELL CYCLE ARREST
Citation:
Luft, J. C., I. J. Benjamin, J B. Garges, AND D J. Dix. HEAT SHOCK FACTOR 1-MEDIATED THERMOTOLERANCE PREVENTS CELL DEATH AND RESULTS IN G2/M CELL CYCLE ARREST. CELL STRESS AND CHAPERONES 6(4):326-336, (2001).
Description:
Mammalian cells respond to stress by activating heat shock transcription factors (e.g., HSF1) that regulate increased synthesis of heat shock proteins (HSPs). HSPs mediate protection from deleterious effects of stress by preventing permanent disruption of normal cellular mitosis, meiosis or differentiation. To further characterize this stress response, transformed wild-type hsf1+/+ and mutant hsf1-/- mouse embryonic fibroblasts (MEFs) were exposed to: 1) lethal heat (451C, 60 minutes), 2) conditioning heat (431C, 30 minutes) or 3) conditioning followed by lethal heat to analyze effects on cell death and cell cycle. Western blot analysis demonstrated only the hsf1+/+ MEFs expressed inducible Hsp70 and Hsp25 following conditioning or conditioning/lethal heat. Exposure of either hsf1+/+ or hsf1-/- MEFs to lethal heat resulted in cell death. However, if conditioning heat was applied 6 hours prior to lethal heat, >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 G2/M accumulation. Co-infection with adenoviral Hsp70 and Hsp25 constructs indicated the necessity of other Hsf1 mediated genes for complete thermotolerance. These results demonstrate the requirement of Hsf1 mediated gene expression for thermotolerance, and thermotolerance involves regulation of the cell cycle.