INSERM U866, Faculty of Medicine and Pharmacy, University of Dijon, Dijon, France.
J Innate Immun. 2010;2(3):238-47. doi: 10.1159/000296508. Epub 2010 Mar 16.
Stress or heat shock proteins (HSPs) 70 and 90 are powerful chaperones whose expression is induced in response to a wide variety of physiological and environmental insults. These proteins have different functions depending on their intracellular or extracellular location. Intracellular HSPs have a protective function. They allow the cells to survive potentially lethal conditions. The cytoprotective functions of HSPs can largely be explained by their anti-apoptotic properties. HSP70 and HSP90 can directly interact with different proteins of the tightly regulated programmed cell death machinery and thereby block the apoptotic process at distinct key points. In cancer cells, where the expression of HSP70 and/or HSP90 is frequently abnormally high, they participate in oncogenesis and in resistance to chemotherapy. Therefore, the inhibition of HSPs has become an interesting strategy in cancer therapy. In contrast to intracellular HSPs, extracellularly located or membrane-bound HSPs mediate immunological functions. They can elicit an immune response providing a link between innate and adaptive immune systems. In cancer, most immunotherapeutical approaches based on extracellular HSPs exploit their carrier function for immunogenic peptides. This review will focus on the roles of HSP70 and HSP90 in apoptosis and in innate immunity and how these functions are being exploited in cancer therapy.
应激或热休克蛋白（HSPs）70 和 90 是强有力的伴侣蛋白，其表达可响应各种生理和环境刺激而诱导。这些蛋白质根据其在细胞内或细胞外的位置具有不同的功能。细胞内 HSP 具有保护功能。它们使细胞能够在潜在致命条件下存活。HSP 的细胞保护功能在很大程度上可以通过其抗细胞凋亡特性来解释。HSP70 和 HSP90 可以直接与严格调节的程序性细胞死亡机制的不同蛋白质相互作用，从而在不同的关键点阻断凋亡过程。在 HSP70 和/或 HSP90 表达频繁异常升高的癌细胞中，它们参与肿瘤发生和化疗耐药。因此，抑制 HSP 已成为癌症治疗中的一种有趣策略。与细胞内 HSP 相反，细胞外定位或膜结合的 HSP 介导免疫功能。它们可以引发免疫反应，在先天和适应性免疫系统之间建立联系。在癌症中，基于细胞外 HSP 的大多数免疫治疗方法利用其载体功能来携带免疫原性肽。这篇综述将重点介绍 HSP70 和 HSP90 在细胞凋亡和固有免疫中的作用，以及这些功能如何在癌症治疗中得到利用。
