Targeted Disruption of Heat Shock Transcription Factor 1 Abolishes Thermotolerance and Protection against Heat-inducible Apoptosis

Heat shock transcription factor 1 (HSF1) is a member of the vertebrate HSF family that regulates stress-inducible synthesis of heat shock proteins (HSPs). Although the synthesis of the constitutively expressed and inducible members of the heat shock family of stress proteins correlates with increase...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-03, Vol.273 (13), p.7523-7528
Main Authors: McMillan, D R, Xiao, X, Shao, L, Graves, K, Benjamin, I J
Format: Article
Language:English
Subjects:
Alleles
Animals
Apoptosis
Base Sequence
Cells, Cultured
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
Fluorescence
Genotype
Heat Shock Transcription Factors
Heat-Shock Proteins - genetics
Heat-Shock Proteins - physiology
Hot Temperature
Mice
Mice, Inbred BALB C
Microscopy, Confocal
Molecular Sequence Data
RNA, Messenger - metabolism
Transcription Factors - genetics
Transcription Factors - physiology
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Summary:Heat shock transcription factor 1 (HSF1) is a member of the vertebrate HSF family that regulates stress-inducible synthesis of heat shock proteins (HSPs). Although the synthesis of the constitutively expressed and inducible members of the heat shock family of stress proteins correlates with increased cellular protection, their relative contributions in acquired cellular resistance or “thermotolerance” in mammalian cells is presently unknown. We report here that constitutive expression of multiple HSPs in cultured embryonic cells was unaffected by disruption of the murine HSF1 gene. In contrast, thermotolerance was not attainable in hsf1 (−/−) cells, and this response was required for protection against heat-induced apoptosis. We conclude that 1) constitutive and inducibly expressed HSPs exhibit distinct physiological functions for cellular maintenance and adaptation, respectively, and 2) other mammalian HSFs or distinct evolutionarily conserved stress response pathways do not compensate for HSF1 in the physiological response to heat shock.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.13.7523