对立的展开蛋白质反应信号汇聚在死亡受体5上,以控制亡
Min Lu1, David A Lawrence1, Scot Marsters1
1Cancer Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
概括
细胞内膜网膜 (ER) 的压力触发了展开的蛋白质反应 (UPR). 持续的UPR激活死亡受体5 (DR5) 诱导细胞亡,将ER压力与细胞死亡联系起来.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 身体生理学 身体生理学
背景情况:
- 蛋白质在细胞内膜网 (ER) 中折叠对细胞功能至关重要.
- ER压力会破坏蛋白质折叠,导致疾病.
- 展开的蛋白质反应 (UPR) 试图恢复ER平衡.
研究的目的:
- 阐明持续ER压力诱导细胞死亡的机制.
- 调查死亡受体5 (DR5) 在ER压力诱导的亡中的作用.
主要方法:
- 研究了UPR调解者CHOP和IRE1α在DR5调节中的作用.
- 在ER压力下分析了DR5转录和mRNA衰变动态.
- 检查了连接体独立的DR5激活和caspase-8参与.
主要成果:
- 未减轻的ER压力通过UPR控制的DR5.5激活细胞自主亡.
- CHOP调解DR5转录,而IRE1α暂时降解DR5mRNA.
- 持续的ER压力导致细胞内DR5蛋白质的积累,导致细胞亡.
结论:
- 在持续的ER压力下,DR5充当了亡的关键调解者.
- 该UPR集成相反的信号来控制DR5表达和细胞命运.
- 激活DR5将ER压力与已编程的细胞死亡途径结合起来.
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