Activation of heat shock genes is not necessary for protection by heat shock transcription factor 1 against cell death due to a single exposure to high temperatures
Activation of heat shock genes is not necessary for protection by heat shock transcription factor 1 against cell death due to a single exposure to high temperatures
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DOI：
10.1128/mcb.23.16.5882-5895.2003
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发表时间：
2003-08-01
影响因子：
5.3
通讯作者：
Nakai, A
中科院分区：
文献类型：
--
作者：
Inouye, S;Katsuki, K;Nakai, A
热休克反应是诱导热耐受的关键，其特征是诱导一系列热休克蛋白，并受热休克转录因子（HSFs）的调节。奇怪的是，HSF 1是哺乳动物热休克反应所必需的，而在禽HSF 3中，热休克基因的爆发激活需要一种禽特异性因子。鸡HSF 1的氨基酸序列与人HSF 1高度保守，但HSF 3的氨基酸序列差异显著。在这里，我们证明了鸡HSF 1失去了通过氨基末端含有富含丙氨酸的序列和DNA结合结构域激活热休克基因的能力。令人惊讶的是，鸡和人的HSF1而不是HSF3具有一种新的功能，可以防止单次暴露于轻度热休克，这不是通过激活热休克基因介导的。不能与DNA结合的HSF1突变体的过表达不能恢复HSF1缺失细胞对细胞死亡的易感性，这表明HSF1的新的保护作用是通过调节热休克基因以外的未知靶基因介导的。这些结果揭示了脊椎动物HSF1的一个新的作用，它已被掩盖下的热休克蛋白的作用。
Heat shock response, which is characterized by the induction of a set of heat shock proteins, is essential for induced thermotolerance and is regulated by heat shock transcription factors (HSFs). Curiously, HSF1 is essential for heat shock response in mammals, whereas in avian HSF3, an avian-specific factor is required for the burst activation of heat shock genes. Amino acid sequences of chicken HSF1 are highly conserved with human HSF1, but those of HSF3 diverge significantly. Here, we demonstrated that chicken HSF1 lost the ability to activate heat shock genes through the amino-terminal domain containing an alanine-rich sequence and a DNA-binding domain. Surprisingly, chicken and human HSF1 but not HSF3 possess a novel function that protects against a single exposure to mild heat shock, which is not mediated through the activation of heat shock genes. Overexpression of HSF1 mutants that could not bind to DNA did not restore the susceptibility to cell death in HSF1-null cells, suggesting that the new protective role of HSF1 is mediated through regulation of unknown target genes other than heat shock genes. These results uncover a novel role of vertebrate HSF1, which has been masked under the roles of heat shock proteins.