Mutated yeast heat shock transcription factor activates transcription independently of hyperphosphorylation
Mutated yeast heat shock transcription factor activates transcription independently of hyperphosphorylation
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DOI：
10.1074/jbc.m510827200
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发表时间：
2006-02-17
影响因子：
4.8
通讯作者：
Sakurai, H
中科院分区：
文献类型：
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作者：
Hashikawa, N;Mizukami, Y;Sakurai, H
同源三聚体热休克转录因子（HSF）与靶基因的热休克元件结合，在不同胁迫条件下调控转录。酿酒酵母Hsf1蛋白在热休克时被广泛磷酸化；这是一种受其c端调节结构域（CTM）积极调节的修饰。过度磷酸化与基因特异性转录激活有关。在这里，我们调查了热休克反应因CTM突变而减少的基因。CTM对于通过单个Hsf1三聚体结合的热休克元件进行转录是必不可少的，但对于通过Hsf1三聚体结合的热休克元件以合作方式进行转录则是必不可少的。位于翼状螺旋-螺旋-螺旋dna结合域的翼区或翼区附近的基因内突变抑制了与CTM突变相关的温度敏感生长表型，并使Hsf1能够独立于超磷酸化激活转录。翅膀的缺失部分恢复了未磷酸化Hsf1的转录缺陷。这些结果证明了超磷酸化和翼区之间的功能联系，并表明这种修饰参与了单个Hsf1三聚体到活性形式的构象变化。
The homotrimeric heat shock transcription factor (HSF) binds to the heat shock element of target genes and regulates transcription in response to various stresses. The Hsf1 protein of Saccharomyces cerevisiae is extensively phosphorylated upon heat shock; a modification that is under positive regulation by its C-terminal regulatory domain (CTM). Hyperphosphorylation has been implicated in gene-specific transcriptional activation. Here, we surveyed genes whose heat shock response is reduced by a CTM mutation. The CTM is indispensable for transcription via heat shock elements bound by a single Hsf1 trimer but is dispensable for transcription via heat shock elements bound by Hsf1 trimers in a cooperative manner. Intragenic mutations located within or near the wing region of the winged helix-turn-helix DNA-binding domain suppress the temperature-sensitive growth phenotype associated with the CTM mutation and enable Hsf1 to activate transcription independently of hyperphosphorylation. Deletion of the wing partially restores the transcriptional defects of the unphosphorylated Hsf1. These results demonstrate a functional link between hyperphosphorylation and the wing region and suggest that this modification is involved in a conformational change of a single Hsf1 trimer to an active form.