Department of Biochemistry, Yamaguchi University School of Medicine, Ube, Japan.
Mol Biol Cell. 2010 Jan 1;21(1):106-16. doi: 10.1091/mbc.e09-07-0639. Epub 2009 Oct 28.
The heat-shock response is characterized by the expression of a set of classical heat-shock genes, and is regulated by heat-shock transcription factor 1 (HSF1) in mammals. However, comprehensive analyses of gene expression have revealed very large numbers of inducible genes in cells exposed to heat shock. It is believed that HSF1 is required for the heat-inducible expression of these genes although HSF2 and HSF4 modulate some of the gene expression. Here, we identified a novel mouse HSF3 (mHSF3) translocated into the nucleus during heat shock. However, mHSF3 did not activate classical heat-shock genes such as Hsp70. Remarkably, overexpression of mHSF3 restored the expression of nonclassical heat-shock genes such as PDZK3 and PROM2 in HSF1-null mouse embryonic fibroblasts (MEFs). Although down-regulation of mHSF3 expression had no effect on gene expression or cell survival in wild-type MEF cells, it abolished the moderate expression of PDZK3 mRNA and reduced cell survival in HSF1-null MEF cells during heat shock. We propose that mHSF3 represents a unique HSF that has the potential to activate only nonclassical heat-shock genes to protect cells from detrimental stresses.
热休克反应的特征是一组经典热休克基因的表达，并在哺乳动物中由热休克转录因子 1（HSF1）调节。然而，对基因表达的综合分析表明，在暴露于热休克的细胞中有大量可诱导的基因。人们认为 HSF1 是这些基因的热诱导表达所必需的，尽管 HSF2 和 HSF4 调节一些基因的表达。在这里，我们鉴定了一种新型的小鼠 HSF3（mHSF3），在热休克期间被转运到核内。然而，mHSF3 并没有激活经典的热休克基因，如 Hsp70。值得注意的是，mHSF3 的过表达在 HSF1 缺失的小鼠胚胎成纤维细胞（MEF）中恢复了非经典热休克基因如 PDZK3 和 PROM2 的表达。虽然 mHSF3 表达下调对野生型 MEF 细胞中的基因表达或细胞存活没有影响，但它在 HSF1 缺失的 MEF 细胞中消除了 PDZK3 mRNA 的适度表达，并降低了细胞在热休克期间的存活。我们提出，mHSF3 代表了一种独特的 HSF，它有可能仅激活非经典的热休克基因来保护细胞免受有害应激。
