Donovan Marissa R, Marr Michael T
From the Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02453.
From the Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02453
J Biol Chem. 2016 Sep 2;291(36):19042-50. doi: 10.1074/jbc.M116.723049. Epub 2016 Jul 19.
Maintaining protein homeostasis is critical for survival at the cellular and organismal level (Morimoto, R. I. (2011) Cold Spring Harb. Symp. Quant. Biol. 76, 91-99). Cells express a family of molecular chaperones, the heat shock proteins, during times of oxidative stress to protect against proteotoxicity. We have identified a second stress responsive transcription factor, dFOXO, that works alongside the heat shock transcription factor to activate transcription of both the small heat shock protein and the large heat shock protein genes. This expression likely protects cells from protein misfolding associated with oxidative stress. Here we identify the regions of the Hsp70 promoter essential for FOXO-dependent transcription using in vitro methods and find a physiological role for FOXO-dependent expression of heat shock proteins in vivo.
维持蛋白质稳态对于细胞和机体水平的生存至关重要（森本，R.I.（2011年）《冷泉港定量生物学研讨会》第76卷，91 - 99页）。在氧化应激期间，细胞会表达一族分子伴侣，即热休克蛋白，以抵御蛋白质毒性。我们鉴定出了第二种应激反应转录因子dFOXO，它与热休克转录因子协同作用，激活小热休克蛋白和大热休克蛋白基因的转录。这种表达可能保护细胞免受与氧化应激相关的蛋白质错误折叠的影响。在这里，我们使用体外方法鉴定了Hsp70启动子中对于FOXO依赖性转录至关重要的区域，并在体内发现了热休克蛋白的FOXO依赖性表达的生理作用。
