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一个新的机制来调节一种转录因子的活性,该因子控制着未折叠的蛋白质反应
1Department of Biochemistry and Biophysics, University of California, School of Medicine, San Francisco 94143-0448, USA.
Cell
|November 1, 1996
概括
细胞通过控制Hac1p水平来激活未折叠蛋白反应 (UPR). 调节的mRNA拼接稳定了Hac1p,一个关键的转录因子,使UPR基因激活.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 细胞拥有机制来管理由未折叠的蛋白质引起的内质网膜 (ER) 压力.
- 展开的蛋白质反应 (UPR) 是一个关键的细胞内信号通路,将ER压力信息传输到细胞核.
研究的目的:
- 确定UPR的关键监管机构.
- 阐明控制转录因子Hac1p的调控机制.
主要方法:
- 在UPR中涉及的转录因子的识别.
- 对Hac1p表达和调节的分析.
- 对mRNA拼接和蛋白质降解途径的研究.
主要成果:
- Hac1p是一种基本的氨酸拉链转录因子,对UPR至关重要.
- 在UPR调节的基因促进剂中,Hac1p与UPR元素结合.
- Hac1p仅存在于UPR激活细胞中,其水平通过受调节的mRNA剪接控制.
- 拼接修改了Hac1p,增加了它对快速依赖于ubiquitin的降解的抵抗力.
结论:
- 对Hac1p表达的复杂调节为UPR提供了多个控制点.
- 调节Hac1p mRNA的拼接是UPR激活的一个关键步骤.
- 通过剪接稳定Hac1p是其在UPR途径中的功能的关键.
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