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由PERK-SRP14轴介导的转位衰减是展开蛋白质反应的保护机制

Yaofu Liu¹, Yuexi Gu², Ying Chen³

¹China Regional Research Centre, International Centre for Genetic Engineering and Biotechnology (ICGEB), Taizhou, Jiangsu 225316, China; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang 310024, China; Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.

|June 29, 2024

概括

展开的蛋白质响应 (UPR) 通过信号识别粒子14 (SRP14) 减少蛋白质转位,以减轻内质网膜 (ER) 压力. 这种依赖PERK的通路通过限制ER压力期间蛋白质的流入来保护细胞.

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:

展开的蛋白质反应 (UPR) 是细胞应激反应对内分泌网膜 (ER) 功能障碍.
UPR涉及减少蛋白质合成,增强蛋白质折叠和降解,以恢复ER平衡.

研究的目的:

研究信号识别粒子14 (SRP14) 在未折叠蛋白反应 (UPR) 中的作用.
阐明SRP14在ER压力期间影响蛋白质转位的机制.

主要方法:

多omics分析以确定ER压力期间蛋白质水平的变化.
研究PERK,eIF2α酸化,ATF4和ATF3在SRP14调控中的作用.
使用融合蛋白和内源性甲素D评估蛋白质转位.
使用具有或没有延伸停止能力的SRP14变体.

主要成果:

在经历ER压力的细胞中,SRP14水平显著降低.
减少SRP14取决于PERK介导的eIF2α酸化,但独立于ATF4/ATF3.3.
降低SRP14与减少的蛋白质转位相关,包括cathepsin D.
SRP14的延长停止能力对于防止减少甲素D转位至关重要.

结论:

PERK-SRP14轴介导转位减弱作为保护UPR机制.
在ER压力期间,SRP14在调节蛋白质转位方面发挥着关键作用.
调节SRP14活动为管理ER压力相关条件提供了潜在的策略.

关键词:

科普:分子生物学分子生物学压力ERER压力ERER压力在 PERK-eIF2α 中.在SRP14中使用SRP14 通过UPR进行全日制检查.卡瑟普辛 D D D D D 信号是一种信号.信号识别粒子的信号识别粒子转位减弱的转位减弱.

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