Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis

被引:415
作者
McMillan, DR
Xiao, XZ
Shao, L
Graves, K
Benjamin, IJ [1 ]
机构
[1] Univ Texas, SW Med Ctr, Dept Internal Med, Mol Cardiol Res Labs, Dallas, TX 75235 USA
[2] Univ Texas, SW Med Ctr, Dept Biochem, Mol Cardiol Res Labs, Dallas, TX 75235 USA
关键词
D O I
10.1074/jbc.273.13.7523
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:7523 / 7528
页数:6
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