蛋白质酶介导的Def1的处理,这是细胞对转录应激反应的关键步骤
Marcus D Wilson1, Michelle Harreman1, Michael Taschner1
1Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms EN6 3LD, UK.
Cell
|September 3, 2013
概括
通过Def1.1,DNA损伤会触发RNA聚合酶II (RNAPII) 的降解. 通过处理,Def1被激活,导致核积累和E3酶的招募,用于RNAPII多基化和蛋白质体分解.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 遗传学 遗传学 是一个
背景情况:
- DNA 损伤激活了一个
- 最后手段的机制.
- 涉及RNA聚合酶II (RNAPII) 的最大子单元的多基化和降解.
- 在酵母中,这个过程依赖于Def1蛋白,但确切的机制仍然不清楚.
研究的目的:
- 阐明之前未解决的机制,即Def1在转录压力期间促进RNAPII降解.
- 详细介绍Def1在对DNA损伤的反应中的激活和功能.
主要方法:
- 通过无处不在和蛋白酶体依赖性处理研究了Def1激活.
- 分析了处理的Def1与RNAPII的局部化和相互作用.
- 描述了Elongin-Cullin E3结合酶复合物的Def1.1的招募.
主要成果:
- Def1激活涉及到无处不在和蛋白酶体依赖的处理,去除一个细胞质局部化域.
- 经过处理的Def1在核中积聚并与RNAPII结合.
- Def1利用其泛素结合域通过Ela1招募Elongin-Cullin E3结合酶复合体,从而促进Rpb1的多泛素化.
结论:
- 在应对转录压力时,Def1充当了Elongin-Cullin泛素酶活性的关键促进剂.
- 通过Def1调解的Rpb1多基化和降解的多步机制已经概述出来.
- Def1处理对于其核定位和随后在触发RNAPII降解中的功能至关重要.
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