BAX抑制因子1是内质网应激传感器IRE1α的负调节因子。
BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha.
作者信息
Lisbona Fernanda, Rojas-Rivera Diego, Thielen Peter, Zamorano Sebastian, Todd Derrick, Martinon Fabio, Glavic Alvaro, Kress Christina, Lin Jonathan H, Walter Peter, Reed John C, Glimcher Laurie H, Hetz Claudio
机构信息
Institute of Biomedical Sciences, FONDAP Center for Molecular Studies of the Cell, University of Chile, Santiago, Chile.
出版信息
Mol Cell. 2009 Mar 27;33(6):679-91. doi: 10.1016/j.molcel.2009.02.017.
Adaptation to endoplasmic reticulum (ER) stress depends on the activation of an integrated signal transduction pathway known as the unfolded protein response (UPR). Bax inhibitor-1 (BI-1) is an evolutionarily conserved ER-resident protein that suppresses cell death. Here we have investigated the role of BI-1 in the UPR. BI-1 expression suppressed IRE1alpha activity in fly and mouse models of ER stress. BI-1-deficient cells displayed hyperactivation of the ER stress sensor IRE1alpha, leading to increased levels of its downstream target X-box-binding protein-1 (XBP-1) and upregulation of UPR target genes. This phenotype was associated with the formation of a stable protein complex between BI-1 and IRE1alpha, decreasing its ribonuclease activity. Finally, BI-1 deficiency increased the secretory activity of primary B cells, a phenomenon regulated by XBP-1. Our results suggest a role for BI-1 in early adaptive responses against ER stress that contrasts with its known downstream function in apoptosis.
对内质网（ER）应激的适应依赖于一种称为未折叠蛋白反应（UPR）的整合信号转导途径的激活。Bax抑制剂-1（BI-1）是一种在进化上保守的内质网驻留蛋白，可抑制细胞死亡。在此，我们研究了BI-1在UPR中的作用。在果蝇和小鼠内质网应激模型中，BI-1的表达抑制了IRE1α的活性。缺乏BI-1的细胞表现出内质网应激传感器IRE1α的过度激活，导致其下游靶点X盒结合蛋白-1（XBP-1）水平升高以及UPR靶基因的上调。这种表型与BI-1和IRE1α之间形成稳定的蛋白质复合物有关，降低了其核糖核酸酶活性。最后，BI-1缺乏增加了原代B细胞的分泌活性，这是一种由XBP-1调节的现象。我们的结果表明，BI-1在针对内质网应激的早期适应性反应中发挥作用，这与其在凋亡中的已知下游功能形成对比。
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