DNAJB3通过与AKT的直接相互作用减轻ER压力
Zeyaul Islam1, Abdoulaye Diane1, Namat Khattab1
1Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar.
PloS one
|August 18, 2023
概括
热冲击蛋白DNAJB3通过与AKT1相互作用,减轻代谢压力和胰岛素抵抗,促进葡萄糖吸收和减轻2型糖尿病中ER压力.
科学领域:
- 分子生物学分子生物学
- 细胞应激反应的应激反应
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 在2型糖尿病 (T2DM) 中的代谢压力降低了像DNAJB3这样的热冲击蛋白 (HSP),从而导致胰岛素抵抗 (IR).
- HSP诱导可以通过抵消代谢压力诱导的信号通路失调来改善胰岛素敏感性.
- 受影响的关键通路包括JNK1,IKKβ,以及随后的IRS-1/IRS-2的无活化,以及PI3K-PKB/AKT通路的激活.
研究的目的:
- 阐明DNAJB3减轻代谢应激并改善葡萄糖平衡的分子机制.
- 研究DNAJB3和AKT1之间的直接相互作用及其功能后果.
- 确定DNAJB3-AKT1相互作用在GLUT4转位和ER应激保护中的作用.
主要方法:
- 蛋白质拉下测试以确定相互作用伙伴.
- 异热定位热量计 (ITC) 用于量化结合亲和力.
- 蛋白质建模和对接以确定结合接口.
- 细胞测试以评估GLUT4转位和ER应激反应.
主要成果:
- DNAJB3与AKT1直接相互作用,其结合亲和力由ITC量化.
- AKT1-DNAJB3复合体定位在细胞质和ER中,促进AS160调动用于葡萄糖运输.
- 通过DNAJB3介导的GLUT4转位和对尼卡米辛诱导的ER压力的保护取决于AKT1的活动.
结论:
- DNAJB3与AKT1直接相互作用,形成一个功能复合体,减轻ER压力.
- 这种相互作用促进GLUT4转位,增强葡萄糖吸收并改善胰岛素敏感性.
- DNAJB3代表了在T2DM中管理代谢压力的潜在治疗标.
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