Yamamoto Noritaka, Maeda Yuka, Ikeda Aya, Sakurai Hiroshi
Division of Health Sciences, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan.
Eukaryot Cell. 2008 May;7(5):783-90. doi: 10.1128/EC.00029-08. Epub 2008 Mar 21.
The heat shock transcription factor Hsf1 and the general stress transcription factors Msn2 and Msn4 (Msn2/4) are major regulators of the heat shock response in Saccharomyces cerevisiae. Here, we show that transcriptional activation of their target genes, including HSP104, an antistress chaperone gene, is obligatory for thermotolerance. Although Hsf1 activity might be necessary before the exposure of cells to high temperature, severe heat shock induced the binding of hyperphosphorylated Hsf1 to its target promoters. However, promoter-bound, phosphorylated Hsf1 was inactive for transcription because RNA polymerase II was inactive at high temperatures. Rather, our results suggest that Hsf1 activates the transcription of most of its target genes during the recovery period following severe heat shock. This delayed upregulation by Hsf1, which would be induced by misfolded proteins that accumulate in severely heat-shocked cells, is required for the resumption of normal cell growth. In contrast, the factors Msn2/4 were not involved in the delayed upregulation of genes and were dispensable for cell growth during the recovery period, suggesting that they play a role before the exposure to high temperature. These results show that Hsf1 and Msn2/4 act differentially before and after exposure to extreme temperatures to ensure cell survival and growth.
热休克转录因子Hsf1以及一般应激转录因子Msn2和Msn4（Msn2/4）是酿酒酵母热休克反应的主要调节因子。在此，我们表明它们的靶基因（包括抗应激伴侣基因HSP104）的转录激活对于耐热性是必不可少的。尽管在细胞暴露于高温之前Hsf1的活性可能是必需的，但严重热休克会诱导过度磷酸化的Hsf1与其靶启动子结合。然而，与启动子结合的磷酸化Hsf1在转录方面是无活性的，因为RNA聚合酶II在高温下无活性。相反，我们的结果表明，Hsf1在严重热休克后的恢复期激活其大多数靶基因的转录。Hsf1的这种延迟上调是由严重热休克细胞中积累的错误折叠蛋白诱导的，是恢复正常细胞生长所必需的。相比之下，Msn2/4因子不参与基因的延迟上调，并且在恢复期对于细胞生长是可有可无的，这表明它们在暴露于高温之前发挥作用。这些结果表明，Hsf1和Msn2/4在暴露于极端温度之前和之后的作用不同，以确保细胞存活和生长。
