A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response.
A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response.
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Ia类磷脂酰肌醇（PI）3-激酶是胰岛素代谢作用的重要介质，由催化亚基（p110α）和调节亚基（p85α）组成。在这里，我们证明，p85α与X-box结合蛋白-1（XBP-1），未折叠蛋白反应（UPR）的转录介质，在ER应激依赖的方式相互作用。p85α基因敲除或敲低的细胞系表现出UPR的显著改变，包括减少ER应激依赖的核XBP-1积累，减少UPR靶基因的诱导和增加细胞凋亡率。这与IRE 1 α和ATF 6 α的活化减少有关。肝脏中p85α缺失的小鼠（L-Pik 3r 1 −/−）在衣霉素给药后显示出类似的减弱的UPR，导致炎症反应增加。因此，p85α在PI 3-激酶途径（胰岛素作用的核心）和细胞对ER应激反应的调节（可导致胰岛素抵抗）之间形成了一种新的联系。
Class Ia phosphoinositide (PI) 3-kinase, an essential mediator of the metabolic actions of insulin, is composed of a catalytic (p110α) and regulatory (p85α) subunit. Here we demonstrate that p85α interacts with X-box binding protein-1 (XBP-1), a transcriptional mediator of the unfolded protein response (UPR), in an ER stress-dependent manner. Cell lines with knockout or knockdown of p85α exhibit dramatic alterations in the UPR including reduced ER stress-dependent accumulation of nuclear XBP-1, decreased induction of UPR target genes and increased rates of apoptosis. This is associated with a decrease activation of IRE1α and ATF6α. Mice with deletion of p85α in liver (L-Pik3r1−/−) display a similar attenuated UPR following tunicamycin administration leading to an increased inflammatory response. Thus, p85α forms a novel link between the PI 3-kinase pathway, which is central to insulin action, and the regulation of the cellular response to ER stress, which can lead to insulin resistance.
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影响因子：
15.9
作者：
Cusi, K;Maezono, K;Mandarino, LJ
通讯作者：
Mandarino, LJ
影响因子：
5.3
作者：
CHEATHAM, B;VLAHOS, CJ;KAHN, CR
通讯作者：
KAHN, CR
DOI：
10.1152/ajpendo.1995.268.4.e604
发表时间：
1995-04-01
影响因子：
5.1
作者：
HEYDRICK, SJ;GAUTIER, N;LEMARCHANDBRUSTEL, Y
通讯作者：
LEMARCHANDBRUSTEL, Y
影响因子：
--
作者：
Gao, ZG;Zhang, XY;Ye, JP
通讯作者：
Ye, JP
影响因子：
64.8
作者：
Calfon, M;Zeng, HQ;Ron, D
通讯作者：
Ron, D