Chonghaile Triona Ni, Gupta Sanjeev, John Mohan, Szegezdi Eva, Logue Susan E, Samali Afshin
Apoptosis Research Centre, National University of Ireland, Galway, Ireland; School of Natural Sciences, National University of Ireland, Galway, Ireland.
Apoptosis Research Centre, National University of Ireland, Galway, Ireland; School of Medicine, National University of Ireland, Galway, Ireland.
Biochem Biophys Res Commun. 2015 Oct 9;466(1):40-5. doi: 10.1016/j.bbrc.2015.08.100. Epub 2015 Aug 28.
Accumulation of unfolded proteins within the endoplasmic reticulum (ER) triggers a highly conserved stress response mechanism termed the unfolded protein response (UPR). The UPR is a complex series of signaling pathways controlled by ER localized transmembrane receptors, PERK, ATF6 and IRE1α. Following activation IRE1α splices XBP-1 mRNA facilitating the formation of a potent transcription factor, spliced XBP-1. The BCL-2 family members, BAX and BAK, in addition to the mitochondrion also localize to the ER and have been demonstrated to directly interact with IRE1α promoting its activity. In this study we show that in addition to BAX and BAK, the anti-apoptotic BCL-2 protein can regulate IRE1α activity. Enhanced splicing of XBP-1 was observed in BCL-2 overexpressing cells implicating BCL-2 in the complex regulation of IRE1α activity.
内质网（ER）中未折叠蛋白的积累触发了一种高度保守的应激反应机制，称为未折叠蛋白反应（UPR）。UPR是由内质网定位的跨膜受体PERK、ATF6和IRE1α控制的一系列复杂信号通路。激活后，IRE1α剪接XBP-1 mRNA，促进强效转录因子剪接XBP-1的形成。BCL-2家族成员BAX和BAK除了定位于线粒体之外，也定位于内质网，并且已证明它们直接与IRE1α相互作用以促进其活性。在本研究中，我们表明除了BAX和BAK之外，抗凋亡BCL-2蛋白也可以调节IRE1α活性。在过表达BCL-2的细胞中观察到XBP-1的剪接增强，这表明BCL-2参与了IRE1α活性的复杂调节。
