在ER应激过程中,CHOP在驱动细胞命运选择中的有益的适应性作用
Kaihua Liu1, Chaoxian Zhao2, Reed C Adajar3
1Interdisciplinary Graduate Program in Human Toxicology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
EMBO reports
|January 4, 2024
概括
众所周知,转录因子CHOP在细胞内网膜应激过程中诱导细胞死亡,但令人惊的是,它也促进了其他细胞的细胞增殖和恢复. 这种双重作用就像一个"压力测试",在生理压力期间确定细胞命运.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 压力反应应激反应
背景情况:
- 细胞应激触发信号通路,影响细胞命运,包括适应或死亡.
- 众所周知,转录因子C/EBP同源蛋白 (CHOP) 主要在内质网膜 (ER) 应激过程中诱导细胞死亡.
- CHOP在细胞适应中的潜在有益作用在很大程度上仍未被探索.
研究的目的:
- 为了研究CHOP在确定细胞命运的多面性作用,在细胞内网膜压力期间.
- 检查CHOP对细胞死亡和适应途径的贡献.
- 要了解CHOP在生理强度的压力下的功能.
主要方法:
- 利用一种新的,转基因的Chop等位基因来实现多功能基因操纵.
- 采用单细胞分析技术,以动态观察细胞反应.
- 应用生理强度的应力来模仿现实世界的条件.
主要成果:
- CHOP表现出矛盾的功能,在一些细胞中促进细胞死亡,在其他细胞中促进细胞增殖.
- CHOP赋予了细胞的压力特异性竞争性增长优势.
- 单细胞动态揭示了CHOP最大限度地激活未折叠的蛋白质反应 (UPR),以解决压力和随后的增殖.
结论:
- 在生理性压力期间,CHOP作为细胞命运的关键调节者,作为细胞调节器.
- 压力测试 压力测试
- CHOP的双重作用平衡细胞死亡和适应,优化细胞恢复.
- 了解CHOP的动态功能是理解细胞对压力的反应的关键.
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