Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis
Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis
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DOI：
10.1074/jbc.273.13.7523
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发表时间：
1998-03-27
影响因子：
4.8
通讯作者：
Benjamin, IJ
中科院分区：
文献类型：
--
作者：
McMillan, DR;Xiao, XZ;Benjamin, IJ
热休克转录因子1（HSF 1）是脊椎动物HSF家族的成员，调节应激诱导的热休克蛋白（HSP）的合成。尽管应激蛋白的热休克家族的组成型表达和诱导型成员的合成与增加的细胞保护相关，但它们在哺乳动物细胞中获得性细胞抗性或“耐热性”中的相对贡献目前尚不清楚。我们在这里报告，在培养的胚胎细胞中的组成型表达的多种热休克蛋白是不受破坏的小鼠HSF 1基因。与此相反，hsf 1（（-/-））细胞不能获得耐热性，这种反应是防止热诱导的细胞凋亡所必需的。我们的结论是：1）组成型和诱导表达的热休克蛋白表现出不同的生理功能，细胞的维持和适应，分别和2）其他哺乳动物的热休克蛋白或不同的进化保守的应激反应途径不补偿热休克蛋白1的生理反应。
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.