结合K29的自由聚比基链会影响核糖体生物发生,并将核糖体蛋白直接输送到核内质量控制区
Harsha Garadi Suresh1, Eric Bonneil2, Benjamin Albert3
1Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.
Molecular cell
|June 13, 2024
概括
积累K29结合的多比基链破坏了核糖体组合,激活了应激反应,导致了蛋白质封存. 这揭示了对核糖体病变机制和细胞毒性的新见解.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 核糖体组装对细胞功能至关重要,需要精确协调组件生产.
- 影响核糖体组合或功能的突变可能导致核糖体病变,通常与蛋白质稳定性缺陷有关.
- 蛋白质稳定酶,包括二维基酶 (DUBs) 和E3酶,在蛋白质质量控制中发挥关键作用.
研究的目的:
- 研究酵母蛋白质稳定酶 (Ubp2,Ubp14,Ufd4,Hul5) 与它们在调节K29结合的多比基链中的作用之间的相互作用.
- 了解这些聚比基链如何影响核糖体组合和细胞反应.
- 探索核内质量控制区 (INQ) 在核糖体病变中的生理相关性.
主要方法:
- 使用了酵母遗传学和分子生物学技术.
- 对二双酸酶 (DUB) 和E3酶活动的分析.
- 检测和量化K29连接的未固的多比基链.
- 评估核糖体组合,核糖体组合应激反应 (RASTR) 激活,以及蛋白质定位到核内质量控制区 (INQ).
主要成果:
- 特定的蛋白质稳定酶调节K29结合的多比基链的细胞水平.
- 积累K29结合的多比基链会破坏成熟的核糖体组合.
- 被破坏的核糖体组装激活核糖体组装应激反应 (RASTR) 并导致INQ中的核糖体蛋白质封存.
- 这些事件凸显了INQ在与核糖体病变相关的细胞毒性中的生理作用.
结论:
- 这项研究阐明了一种新的机制,它将蛋白质稳定,多比基因化和核糖体生物发生联系起来.
- 与K29结合的聚比基链作为一个信号,破坏了核糖体组合,并触发了细胞应激反应.
- 这些发现提供了关于核糖体病变的发病过程和INQ的功能的关键见解.
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