内质网膜应激对减少哺乳动物细胞中重组蛋白质生产的作用
R Chauncey Splichal1, Kevin Chen1, S Patrick Walton1
1Department of Chemical Engineering and Materials Science, Michigan State University, MI, USA.
Biochemical engineering journal
|September 2, 2024
概括
细胞内膜网膜 (ER) 的压力会影响蛋白质折叠,DNA修复和分泌,从而损害治疗性蛋白质的产生. 管理ER压力对于哺乳动物细胞培养中的高效重组蛋白制造至关重要.
科学领域:
- 生物技术是生物技术.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 哺乳动物细胞中的重组蛋白质生产面临着由于细胞压力的挑战.
- 细胞内膜网膜 (ER) 压力是由于蛋白质合成机器的压力而产生的,导致蛋白质展开.
- ER压力触发了未折叠的蛋白质反应 (UPR) 来恢复蛋白质静止,涉及改变的蛋白质合成,降解和潜在的亡.
研究的目的:
- 审查ER应激和对蛋白质生产和分泌至关重要的过程之间的关联.
- 阐明ER压力如何影响重组蛋白质产量和质量.
- 在细胞培养中突显ER蛋白质稳定和DNA损伤修复 (DDR) 之间的相互作用.
主要方法:
- 文献综述侧重于ER压力,UPR,蛋白质稳定和DDR途径.
- 分析细胞压力如何影响蛋白质合成,折叠,修饰和分泌.
- 检查ER压力对基因组稳定性和细胞活力的影响.
主要成果:
- ER压力通过抑制全球蛋白转化和减少伴侣合成,显著影响重组蛋白生产.
- 错误折叠的蛋白质降解途径和自在ER压力下升级,可能降低蛋白质产量.
- 在ER压力和DDR路径之间的交叉影响基因组完整性,细胞活力,因此,蛋白质的生产.
结论:
- ER压力通过多种细胞机制对重组蛋白质生产产生负面影响,包括蛋白质分泌量减少和DNA修复受损.
- 维持蛋白质静止和减轻ER压力对于优化治疗性蛋白质制造至关重要.
- 了解ER压力与基因组稳定性之间的联系对于改善基于细胞的蛋白质生产系统至关重要.
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