在乳腺癌细胞中,RHBDF1通过JNK/FoxO3通路促进PERK的表达
SungJu Ryu1,2, Hui Long3, Xiaojing Quan1
1State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, and the Haihe Laboratory of Cell Ecosystem, Tianjin 300350, China.
RHBDF1基因对乳腺癌细胞存活至关重要,因为它通过维持内细胞网膜 (ER) 蛋白质平衡来维持乳腺癌细胞的存活. 它通过PERK通路调节未折叠蛋白质响应 (UPR),这对ER稳态至关重要.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- RHBDF1基因被认为是乳腺癌的一个瘤基因.
- RHBDF1在细胞内膜网膜 (ER) 蛋白质稳态和未折叠蛋白质反应 (UPR) 中发挥作用.
研究的目的:
- 调查RHBDF1和ER应力传感器 (PERK,IRE1,ATF6) 之间的关系.
- 阐明 RHBDF1 影响 UPR 和 ER 蛋白质稳态的机制.
主要方法:
- 在乳腺癌细胞中研究RHBDF1缺乏和过度表达.
- 分析了ER应激通路组件 (PERK,pPERK,peIF2α,IRE1,ATF6) 的蛋白质水平.
- 研究了JNK和FoxO3在RHBDF1-介导的UPR信号传输中的作用.
主要成果:
- 缺乏RHBDF1导致乳腺癌细胞中PERK,pPERK和peIF2α水平降低.
- 过度表达RHBDF1,但不是IRE1或ATF6,恢复了这些蛋白质水平.
- RHBDF1激活了JNK,导致了FoxO3的核转移和PERK的产生.
结论:
- RHBDF1通过JNK/FoxO3轴对PERK/peIF2α通路进行上调,以支持UPR.
- 在乳腺癌细胞中,RHBDF1的功能对于维持ER蛋白的恒常性至关重要.
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