Anckar Julius, Sistonen Lea
Department of Biology, Abo Akademi University, P.O. Box 123 FI-20521 Turku, Finland.
Adv Exp Med Biol. 2007;594:78-88. doi: 10.1007/978-0-387-39975-1_8.
The transition from normal growth conditions to stressful conditions is accompanied by a robust upregulation of heat shock proteins, which dampen the cytotoxicity caused by misfolded and denatured proteins. The most prominent part of this transition occurs on the transcriptional level. In mammals, protein-damaging stress leads to the activation of heat shock factor 1 (HSF1), which binds to upstream regulatory sequences in the promoters of heat shock genes. The activation of HSF1 proceeds through a multi-step pathway, involving a monomer-to-trimer transition, nuclear accumulation and extensive posttranslational modifications. In addition to its established role as the main regulator of heat shock genes, new data link HSF 1 to developmental pathways. In this chapter, we examine the established stress-related functions and prospect the intriguing role of HSF 1 as a developmental coordinator.
从正常生长条件转变为应激条件时,热休克蛋白会大量上调,从而减轻错误折叠和变性蛋白所导致的细胞毒性。这种转变最显著的部分发生在转录水平。在哺乳动物中,蛋白质损伤应激会导致热休克因子1(HSF1)激活,该因子会与热休克基因启动子中的上游调控序列结合。HSF1的激活通过多步骤途径进行,包括单体到三聚体的转变、核积累以及广泛的翻译后修饰。除了作为热休克基因的主要调节因子这一既定作用外,新数据还将HSF1与发育途径联系起来。在本章中,我们将研究与应激相关的既定功能,并展望HSF1作为发育协调因子的有趣作用。