Novel isoforms of heat shock transcription factor 1, HSF1γα and HSF1γβ, regulate chaperone protein gene transcription.
Novel isoforms of heat shock transcription factor 1, HSF1γα and HSF1γβ, regulate chaperone protein gene transcription.
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DOI：
10.1074/jbc.m114.570739
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发表时间：
2014-07-18
期刊：
影响因子：
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通讯作者：
Bates GP
中科院分区：
文献类型：
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作者：
Neueder A;Achilli F;Moussaoui S;Bates GP
背景：热休克因子1（HSF1）是调节热休克蛋白基因表达的主要真核转录因子。结果：我们确定了两个新的HSF 1亚型，并显示HSF 1亚型差异调节伴侣基因转录。结论：HSF 1亚型具有协同作用，HSF 1亚型的比例决定了伴侣基因的转录水平。意义：我们的研究结果揭示了通过HSF1亚型比例调节HSP表达的另一层伴侣基因调控。热休克反应，导致热休克蛋白或分子伴侣的产生，是由升高的温度和各种其他应激源触发的。它的主要调节因子是热休克转录因子1（HSF 1）。热休克因子通常以多种异构体存在。两种已知的HSF 1亚型的区别在于外显子11的包含（HSF 1 α）或排除（HSF 1 β）。虽然有一些数据有关的差异表达模式和转录活性的HSF 2亚型在发展过程中，鲜为人知的是独特的性质的HSF 1亚型。在这里，我们提出了两种新的HSF 1亚型的证据，称为HSF 1 γα和HSF 1 γβ，我们表明，HSF 1亚型的比例差异调节热休克蛋白基因转录。Hsf1γ亚型在多种小鼠组织中表达并翻译成蛋白质。此外，热休克后，HSF 1 γ亚型比HSF 1 α或HSF 1 β更快地从细胞核输出或降解。我们还表明，每个单独的HSF 1亚型足以诱导热休克反应，并且HSF 1亚型的组合，特别是HSF 1 α和HSF 1 β的表达，导致转录反应的协同增强。此外，HSF 1 γ亚型可能抑制HSF 1 α和HSF 1 β共表达的协同效应。总的来说，我们的观察表明，HSF 1亚型的表达在一个特定的比例提供了一个额外的层在调节热休克蛋白基因转录。
Background: HSF1 is the major eukaryotic transcription factor that regulates expression of HSP genes. Results: We identify two novel HSF1 isoforms and show that HSF1 isoforms differentially regulate chaperone gene transcription. Conclusion: HSF1 isoforms work synergistically, and the ratio of HSF1 isoforms determines chaperone gene transcription levels. Significance: Our findings unravel an additional layer of chaperone gene regulation through modulation of HSP expression by HSF1 isoform ratios. The heat shock response, resulting in the production of heat shock proteins or molecular chaperones, is triggered by elevated temperature and a variety of other stressors. Its master regulator is heat shock transcription factor 1 (HSF1). Heat shock factors generally exist in multiple isoforms. The two known isoforms of HSF1 differ in the inclusion (HSF1α) or exclusion (HSF1β) of exon 11. Although there are some data concerning the differential expression patterns and transcriptional activities of HSF2 isoforms during development, little is known about the distinct properties of the HSF1 isoforms. Here we present evidence for two novel HSF1 isoforms termed HSF1γα and HSF1γβ, and we show that the HSF1 isoform ratio differentially regulates heat shock protein gene transcription. Hsf1γ isoforms are expressed in various mouse tissues and are translated into protein. Furthermore, after heat shock, HSF1γ isoforms are exported from the nucleus more rapidly or degraded more quickly than HSF1α or HSF1β. We also show that each individual HSF1 isoform is sufficient to induce the heat shock response and that expression of combinations of HSF1 isoforms, in particular HSF1α and HSF1β, results in a synergistic enhancement of the transcriptional response. In addition, HSF1γ isoforms potentially suppress the synergistic effect of HSF1α and HSF1β co-expression. Collectively, our observations suggest that the expression of HSF1 isoforms in a specific ratio provides an additional layer in the regulation of heat shock protein gene transcription.