Arrigo A P
Laboratoire du stress cellulaire, centre de génétique moléculaire et cellulaire, CNRS-UMR-5534, université Claude-Bernard Lyon-I, Villeurbanne, France.
Pathol Biol (Paris). 2000 Apr;48(3):280-8.
sHsp (small stress proteins) are molecular chaperones involved in cellular defence mechanisms against several different types of aggressions. These proteins also participate in essential physiological processes, such as regulation of cell cycle, differentiation, programmed cell death and tumorigenicity. For example, sHsp are transiently expressed during the cell division to differentiation transition and this phenomenon prevents differentiating cells from undergoing apoptosis. sHsp also protect against apoptosis induced by different conditions or agents, particularly anti-cancer drugs. Of interest, tumor cells usually express high levels of sHsp, and anti-cancer drugs, such as cisplatin, trigger the accumulation of sHsp. These proteins are also known to interfere with programmed cell death induced by TNF alpha and Fas ligand. Moreover, they enhance the growth of tumors in vivo. Taken together, these observations suggest that sHsp can allow cancerous cells to escape the immunosurveillance mediated by death ligands and can render these cells resistant to therapy. Hence, sHsp represent prime targets for therapeutic interventions. This review is focused on the role of sHsp in different aspects of the life and death of mammalian cells and on the role of these survival proteins in cancer.
小分子热休克蛋白（sHsp）是参与细胞抵御多种不同类型侵害的分子伴侣。这些蛋白质还参与重要的生理过程，如细胞周期调控、分化、程序性细胞死亡和肿瘤发生。例如，sHsp在细胞从分裂向分化转变过程中短暂表达，这种现象可防止分化中的细胞发生凋亡。sHsp还能保护细胞免受不同条件或因子诱导的凋亡，尤其是抗癌药物。有趣的是，肿瘤细胞通常高水平表达sHsp，而抗癌药物如顺铂会引发sHsp的积累。这些蛋白质还已知会干扰由肿瘤坏死因子α（TNFα）和Fas配体诱导的程序性细胞死亡。此外，它们会促进体内肿瘤的生长。综上所述，这些观察结果表明，sHsp可使癌细胞逃避死亡配体介导的免疫监视，并使这些细胞对治疗产生抗性。因此，sHsp是治疗干预的主要靶点。本综述聚焦于sHsp在哺乳动物细胞生死不同方面的作用以及这些存活蛋白在癌症中的作用。
