以ECPAS/Ecm29为媒介的26S蛋白质酶分解是对葡萄糖饥饿的适应性反应
Won Hoon Choi1, Yejin Yun2, Insuk Byun2
1Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea.
Cell reports
|June 29, 2023
概括
葡萄糖饥饿导致26S蛋白质组分裂为20S和19S部分,这是由Ecm29蛋白质组适配器和支架 (ECPAS) 介导的过程. 这种解体有助于细胞通过改变蛋白质分解来应对压力.
科学领域:
- 细胞生物学 细胞生物学
- 分子机制的分子机制
- 生物化学 生化学
背景情况:
- 由20S催化和19S调节复合体组成的26S蛋白酶体存在于细胞中,其自由20S复合体约为半个.
- 控制26S与20S蛋白酶体物种的比率的精确机制尚未完全理解.
研究的目的:
- 为了研究26S与20S蛋白酶体物种的比率的机制基础.
- 阐明葡萄糖可用性和特定蛋白质因子在蛋白质酶体结构动态中的作用.
主要方法:
- 亚复杂的亲和力净化与定量质谱相结合.
- 蛋白质构造变化的模型模型.
- 在葡萄糖饥饿下对蛋白酶体活性和基质降解的分析.
- 在缺乏葡萄糖条件下的瘤体内异种移植研究.
主要成果:
- 葡萄糖饥饿诱导26S全酶解成20S和19S亚复合体.
- Ecm29蛋白酶体适配器和支架 (ECPAS) 被确定为这种结构重塑的媒介.
- 失去ECPAS可以防止26S解离,从而减少20S蛋白酶基质的降解.
- 在葡萄糖饥饿期间,ECPAS对内质网膜应激反应和细胞存活至关重要.
- 在体内,在缺乏葡萄糖的瘤中观察到20S蛋白酶水平升高.
结论:
- 20S-19S蛋白酶体分解是一种调节的机制,使全球蛋白质分解适应生理条件,例如葡萄糖饥饿.
- 这一过程对于应对蛋白质毒性压力和确保细胞存活至关重要.
- 在应对细胞压力时,ECPAS在调解蛋白质体结构可塑性方面发挥着至关重要的作用.
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