Akerfelt Malin, Trouillet Diane, Mezger Valérie, Sistonen Lea
Turku Centre for Biotechnology, P.O. Box 123, FI-20521 Turku, Finland.
Ann N Y Acad Sci. 2007 Oct;1113:15-27. doi: 10.1196/annals.1391.005. Epub 2007 May 4.
Organisms must be able to sense and respond rapidly to changes in their environment in order to maintain homeostasis and survive. Induction of heat shock proteins (Hsps) is a common cellular defense mechanism for promoting survival in response to various stress stimuli. Heat shock factors (HSFs) are transcriptional regulators of Hsps, which function as molecular chaperones in protecting cells against proteotoxic damage. Mammals have three different HSFs that have been considered functionally distinct: HSF1 is essential for the heat shock response and is also required for developmental processes, whereas HSF2 and HSF4 are important for differentiation and development. Specifically, HSF2 is involved in corticogenesis and spermatogenesis, and HSF4 is needed for maintenance of sensory organs, such as the lens and the olfactory epithelium. Recent evidence, however, suggests a functional interplay between HSF1 and HSF2 in the regulation of Hsp expression under stress conditions. In lens formation, HSF1 and HSF4 have been shown to have opposite effects on gene expression. In this chapter, we present the different roles of the mammalian HSFs as regulators of cellular stress and developmental processes. We highlight the interaction between different HSFs and discuss the discoveries of novel target genes in addition to the classical Hsps.
生物体必须能够快速感知并响应其环境变化，以维持体内平衡并生存。热休克蛋白（Hsps）的诱导是一种常见的细胞防御机制，用于在应对各种应激刺激时促进生存。热休克因子（HSFs）是Hsps的转录调节因子，其作为分子伴侣发挥作用，保护细胞免受蛋白毒性损伤。哺乳动物有三种不同的HSFs，它们在功能上被认为是不同的：HSF1对热休克反应至关重要，也是发育过程所必需的，而HSF2和HSF4对分化和发育很重要。具体而言，HSF2参与皮质发生和精子发生，而HSF4是维持感觉器官（如晶状体和嗅觉上皮）所必需的。然而，最近的证据表明，在应激条件下，HSF1和HSF2在Hsp表达的调节中存在功能相互作用。在晶状体形成过程中，HSF1和HSF4对基因表达表现出相反的作用。在本章中，我们介绍了哺乳动物HSFs作为细胞应激和发育过程调节因子的不同作用。我们强调了不同HSFs之间的相互作用，并讨论了除经典Hsps之外新靶基因的发现。
