Defining the Essential Function of Yeast Hsf1 Reveals a Compact Transcriptional Program for Maintaining Eukaryotic Proteostasis.
Defining the Essential Function of Yeast Hsf1 Reveals a Compact Transcriptional Program for Maintaining Eukaryotic Proteostasis.
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DOI：
10.1016/j.molcel.2016.05.014
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发表时间：
2016-07-07
期刊：
影响因子：
16
通讯作者：
Denic V
中科院分区：
文献类型：
--
作者：
Solís EJ;Pandey JP;Zheng X;Jin DX;Gupta PB;Airoldi EM;Pincus D;Denic V
尽管其与热休克反应的关系密切，但酵母热休克因子1（Hsf1）即使在低温下也是必不可少的。在这里，我们表明，工程核出口的Hsf1的结果与大量的蛋白质聚集的细胞毒性。全基因组分析表明，Hsf1核出口立即降低基础转录和mRNA表达的18个基因，主要编码伴侣。引人注目的是，拯救Hsp70和Hsp90分子伴侣的基础表达能够在完全不存在Hsf1的情况下实现稳健的细胞生长。除了伴侣基因诱导，绝大多数的热休克反应是Hsf1独立的。通过对哺乳动物细胞系的比较分析，我们发现只有热休克诱导的而不是基础的伴侣蛋白表达依赖于哺乳动物Hsf1同源物（HSF1）。我们的工作表明，酵母伴侣基因表达是一个重要的管家机制，并提供了一个路线图定义的功能HSF1作为一个驱动程序的肿瘤发生。
Despite its eponymous association with the heat shock response, yeast heat shock factor 1 (Hsf1) is essential even at low temperatures. Here we show that engineered nuclear export of Hsf1 results in cytotoxicity associated with massive protein aggregation. Genome-wide analysis revealed that Hsf1 nuclear export immediately decreased basal transcription and mRNA expression of 18 genes, which predominately encode chaperones. Strikingly, rescuing basal expression of Hsp70 and Hsp90 chaperones enabled robust cell growth in the complete absence of Hsf1. With the exception of chaperone gene induction, the vast majority of the heat shock response was Hsf1-independent. By comparative analysis of mammalian cell lines, we found that only heat shock-induced but not basal expression of chaperones is dependent on the mammalian Hsf1 homolog (HSF1). Our work reveals that yeast chaperone gene expression is an essential housekeeping mechanism and provides a roadmap for defining the function of HSF1 as a driver of oncogenesis.