爱尔兰国立大学（高威）的研究人员一项最新发现表明，一种蛋白能够使细胞在承受强烈压力的情况下存活。因此，理解该机制或能有助于科学家干预癌细胞，使其不能在压力环境下存活，并开发出针对一些疾病来说更为有效的疗法。
这项研究结果发布在PLoS Biology杂志的在线版本上。
健康的细胞通常不会面临压力，但是不健康的细胞，比如癌细胞，通常会承受相当的压力，因为它们在不属于自己的"领地"快速生长。当某一细胞处在这些压力环境下时，"压力蛋白"Hsp70就会被激活帮助细胞面对压力躲避灾难。
这项研究的负责人Afshin Samali教授表示，在压力环境下，Hsp70会和细胞中的一个受体互作，激活生存机制，防止细胞发生死亡。对Hsp70蛋白机制的深入理解，比如其执行功能的方式，有助于他们研究阻碍该蛋白发挥功能的策略，使非健康细胞屈服于压力而最终死亡。这对于抗癌新药的开发将是十分有意义的，阻止Hsp70蛋白功能使得肿瘤细胞死亡。相比之下，对于那些存在大量细胞死亡的疾病，比如阿兹海默症，帕金森氏症，糖尿病等，适当增加Hsp70蛋白的水平将帮助这些细胞在压力环境下存活。
这项研究识别了一种新的蛋白-蛋白互作，而该互作使得癌细胞能够承受有压力的生长环境，因此科学家十分希望能够通过干扰该互作开发一类新的抗癌药物。
推荐原文出处：
PLoS biology doi:10.1371/journal.pbio.1000410
HSP72 Protects Cells from ER Stress-induced Apoptosis via Enhancement of IRE1α-XBP1 Signaling through a Physical Interaction
Sanjeev Gupta1#, Ayswaria Deepti1#, Shane Deegan1, Fernanda Lisbona2, Claudio Hetz2, Afshin Samali1*
1 Apoptosis Research Centre, School of Natural Sciences, NUI Galway, Galway, Ireland, 2 Institute of Biomedical Sciences, FONDAP Center for Molecular Studies of the Cell, University of Chile, Santiago, Chile
Endoplasmic reticulum (ER) stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR). Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1α, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1α or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1α. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1α in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1α enhances IRE1α/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.
