乙转移酶EP300和蛋白质体系统在调节热冲击转录因子1中的相互作用
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Swasti Raychaudhuri1, Christian Loew1, Roman Körner1
1Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Cell
|March 4, 2014
概括
哺乳动物细胞激活应激反应以维持蛋白质稳态,涉及热冲击转录因子1 (HSF1). 这项研究确定EP300和核蛋白酶体是HSF1活动和应激反应的关键调节者.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 应激反应机制 应激反应机制
背景情况:
- 哺乳动物细胞在蛋白质毒性条件下激活细胞质应激反应,以维持蛋白质平衡.
- 热冲击转录因子1 (HSF1) 依赖的伴侣表达对于这种反应至关重要.
研究的目的:
- 在HeLa细胞中使用RNA干扰屏幕识别应激反应诱导和减弱的调节器.
- 阐明已识别的蛋白质在HSF1介导的应激反应中的调节作用.
主要方法:
- 在HeLa细胞中的RNA干扰 (RNAi) 屏幕.
- 分析蛋白质局部化和细胞区内的功能.
- 研究HSF1乙化和蛋白质体降解途径.
主要成果:
- 调节蛋白存在于各种细胞区,突出的是染色质修饰剂和核蛋白质质量控制.
- 乙转移酶EP300通过非功能性lysine乙化稳定可激活的HSF1,防止蛋白质体降解.
- 关键氨酸的乙化在压力期间微调HSF1激活.
- 核蛋白酶体系统通过降解与错误折叠蛋白质清除相关的激活HSF1来减弱应激反应.
结论:
- 通过调节HSF1活动,EP300和核蛋白酶是细胞应激反应的关键调节者.
- HSF1调节涉及通过乙化稳定和通过蛋白质体降解减弱之间的平衡.
- 了解这些机制,可以了解在压力下维持蛋白质平衡的方法.
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