愛爾蘭國立大學(xué)（高威）的研究人員一項最新發(fā)現(xiàn)表明，一種蛋白能夠使細胞在承受強烈壓力的情況下存活,。因此,，理解該機制或能有助于科學(xué)家干預(yù)癌細胞，使其不能在壓力環(huán)境下存活,，并開發(fā)出針對一些疾病來說更為有效的療法,。

這項研究結(jié)果發(fā)布在PLoS Biology雜志的在線版本上。

健康的細胞通常不會面臨壓力,，但是不健康的細胞,，比如癌細胞，通常會承受相當(dāng)?shù)膲毫?，因為它們在不屬于自己?quot;領(lǐng)地"快速生長,。當(dāng)某一細胞處在這些壓力環(huán)境下時，"壓力蛋白"Hsp70就會被激活幫助細胞面對壓力躲避災(zāi)難,。

這項研究的負責(zé)人Afshin Samali教授表示,，在壓力環(huán)境下，Hsp70會和細胞中的一個受體互作,，激活生存機制,，防止細胞發(fā)生死亡。對Hsp70蛋白機制的深入理解,，比如其執(zhí)行功能的方式,，有助于他們研究阻礙該蛋白發(fā)揮功能的策略，使非健康細胞屈服于壓力而最終死亡,。這對于抗癌新藥的開發(fā)將是十分有意義的,，阻止Hsp70蛋白功能使得腫瘤細胞死亡。相比之下，對于那些存在大量細胞死亡的疾病,，比如阿茲海默癥,，帕金森氏癥，糖尿病等,，適當(dāng)增加Hsp70蛋白的水平將幫助這些細胞在壓力環(huán)境下存活,。

這項研究識別了一種新的蛋白-蛋白互作，而該互作使得癌細胞能夠承受有壓力的生長環(huán)境,，因此科學(xué)家十分希望能夠通過干擾該互作開發(fā)一類新的抗癌藥物,。(生物谷Bioon.net)

更多閱讀點擊 生物谷 www.bioon.net

生物谷推薦原文出處：

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.