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在哺乳动物中,N-recognins将UBR1和UBR2视为中央ER应激传感器
Ly Thi Huong Luu Le1, Seoyoung Park2, Jung Hoon Lee3
1Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea.
Molecules and cells
|February 20, 2024
概括
这是N-degron路径.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 蛋白质降解 蛋白质降解
背景情况:
- 蛋白质质量控制 (PQC) 对于细胞功能至关重要,其中内分泌网膜 (ER) 起着关键作用.
- 与ER相关的降解 (ERAD) 消除了错误折叠的蛋白质,但许多E3泛素酶在这个过程中的作用仍然不清楚.
- 涉及N-识别素的N-降解途径对蛋白质的稳定性和降解至关重要.
研究的目的:
- 为了研究在ER应激反应中Ubiquitin蛋白质合酶E3成分N-recognin1 (UBR1) 和Ubiquitin蛋白质合酶E3成分N-recognin2 (UBR2) 的作用.
- 确定UBR1和UBR2在哺乳动物蛋白质质量控制中的参与.
- 在ER应力条件下阐明UBR1和UBR2的稳定性调制.
主要方法:
- 确定UBR1和UBR2作为N-降解通路中的关键N-识别素.
- 对缺乏UBR1和UBR2的细胞中ER应激的细胞反应的分析.
- 通过26S蛋白酶体对UBR1和UBR2的泛化和降解的研究.
主要成果:
- 缺乏UBR1和UBR2的细胞对ER压力诱导的亡过敏.
- 在正常条件下,UBR1和UBR2被多基化 (Lys48特异性) 并被26S蛋白质组降解.
- ER压力增加了UBR1和UBR2的稳定性,这表明细胞有适应性反应.
结论:
- 细胞质UBR1和UBR2具有抗ER应激活性,并有助于哺乳动物的全球PQC.
- N-degron通路涉及哺乳动物的ERAD系统,增加了蛋白质质量控制的复杂性.
- UBR1和UBR2稳定性调制代表了ER应激反应的新方面.
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