JAB1 participates in unfolded protein responses by association and dissociation with IRE1
JAB1 participates in unfolded protein responses by association and dissociation with IRE1
复制标题
DOI：
10.1016/j.neuint.2004.01.003
复制
发表时间：
2004-10-01
影响因子：
4.2
通讯作者：
Tohyama, M
中科院分区：
文献类型：
--
作者：
Oono, K;Yoneda, T;Tohyama, M
最近的论文报道，阿尔茨海默病、帕金森病和脑缺血患者的神经元死亡起源于内质网（ER）。IRE批次是检测ER中未折叠蛋白积聚的ER应力传感器之一。IRE1 α介导两种主要的细胞反应，即未折叠蛋白反应（UPR）（一种防御反应）和导致细胞死亡的凋亡。然而，很少有人知道的调节机制，选择之间的UPR和凋亡。我们使用酵母双杂交系统鉴定了Jun激活结构域结合蛋白1（JAB 1）作为与IRE1 α相互作用的分子。我们证明，JAB 1结合IRE1 α在应力的情况下，但结合减少ER应力诱导剂。此外，突变JAB 1通过与IRE1 α紧密结合下调UPR信号通路。这些结果表明，JAB 1可能是通过与IRE I结合和解离而选择UPR或细胞死亡的关键分子。(C)2004爱思唯尔有限公司保留所有权利。
Recent papers have reported that neuronal death in patients with Alzheimer's disease, Parkinson's disease, and cerebral ischemia has its origin in the endoplasmic reticulum (ER). IRE lot is one of the ER stress transducers that detect the accumulation of unfolded proteins in the ER. IRE1alpha mediates two major cellular responses, which are the unfolded protein response (UPR), a defensive response, and apoptosis that leads to cell death. However, little is known about the regulatory mechanisms that select between the UPR and apoptosis. We identified Jun activation domain-binding protein-1 (JAB1) as a molecule that interacts with IRE1alpha using a yeast two-hybrid system. We demonstrated that JAB1 binds to IRE1alpha in the absence of stress, but that binding is decreased by ER stress inducers. Moreover, mutant JAB1 down-regulates the UPR signaling pathway through tight binding with IRE1alpha. These results suggested that JAB1 may act as a key molecule in selecting the UPR or cell death by association and dissociation with IRE I (X. (C) 2004 Elsevier Ltd. All rights reserved.