Schmitt E, Gehrmann M, Brunet M, Multhoff G, Garrido C
INSERM U-517, 7 Boulevard Jeanne d'Arc, Faculty of Medicine and Pharmacy, Dijon 21079, France, and Department of Hematology/Oncology, University Hospital Regensburg, Germany.
J Leukoc Biol. 2007 Jan;81(1):15-27. doi: 10.1189/jlb.0306167. Epub 2006 Aug 24.
Stress or heat shock proteins (HSPs) are the most conserved proteins present in both prokaryotes and eukaryotes. Their expression is induced in response to a wide variety of physiological and environmental insults. These proteins play an essential role as molecular chaperones by assisting the correct folding of nascent and stress-accumulated misfolded proteins, and preventing their aggregation. HSPs have a dual function depending on their intracellular or extracellular location. Intracellular HSPs have a protective function. They allow the cells to survive lethal conditions. Various mechanisms have been proposed to account for the cytoprotective functions of HSPs. Several HSPs have also been demonstrated to directly interact with various components of the tightly regulated programmed cell death machinery, upstream and downstream of the mitochondrial events. On the other hand, extracellular located or membrane-bound HSPs mediate immunological functions. They can elicit an immune response modulated either by the adaptive or innate immune system. This review will focus on HSP27, HSP70, and HSP90. We will discuss the dual role of these HSPs, protective vs. immunogenic properties, making a special emphasis in their utility as targets in cancer therapy.
应激或热休克蛋白（HSPs）是原核生物和真核生物中最保守的蛋白质。它们的表达是在对多种生理和环境损伤作出反应时被诱导产生的。这些蛋白质作为分子伴侣发挥着至关重要的作用，通过协助新生蛋白质和应激积累的错误折叠蛋白质正确折叠，并防止它们聚集。根据其在细胞内或细胞外的位置，热休克蛋白具有双重功能。细胞内热休克蛋白具有保护功能。它们使细胞能够在致命条件下存活。已经提出了各种机制来解释热休克蛋白的细胞保护功能。还证实了几种热休克蛋白可直接与严格调控的程序性细胞死亡机制的各种组分相互作用，这些组分在线粒体事件的上游和下游。另一方面，位于细胞外或膜结合的热休克蛋白介导免疫功能。它们可以引发由适应性或先天性免疫系统调节的免疫反应。本综述将重点关注热休克蛋白27、热休克蛋白70和热休克蛋白90。我们将讨论这些热休克蛋白的双重作用，即保护与免疫原性特性，并特别强调它们作为癌症治疗靶点的效用。
