类激素通过激活依赖于ubiquitin的蛋白质溶解途径来加速它们的吸收
G C Turner1, F Du, A Varshavsky
1Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Nature
|June 13, 2000
概括
像二酸这样的小分子可以调节蛋白质降解. 在酵母中,二激活了Ubr1酶,加速了Cup9的分解,并促进了进口.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 乌比基系统通过26S蛋白质酶体的降解来调节蛋白质水平.
- 像酵母中的Ubr1一样,E3链酶识别蛋白质基板上的降解信号 (降解子).
- Ubr1对于N端规则通路至关重要,通过特定的N端残留物降解蛋白质.
研究的目的:
- 为了研究小化合物对依赖于乌比奎的路径的生理调节.
- 阐明Ubr1在调节Cup9降解中的作用,Cup9是载体Ptr2.2的抑制剂.
- 了解二酸如何影响N端规则通路和酸运输.
主要方法:
- 研究了Saccharomyces cerevisiae中的N端规则通路.
- 研究了Ubr1,Cup9和二之间的相互作用.
- 分析了Ubr1由含有破坏稳定的N端残留物的二酸的全激活.
主要成果:
- 证明了具有破坏稳定的N端残留的二酸会以全质方式激活Ubr1.1.
- 表明这种激活加速了转录抑制剂Cup9.9的降解.
- 确定了一个积极的反循环,其中进口的二增强了通过去压抑Ptr2.2来增强的运输.
结论:
- 小型化合物,特别是二,可以在生理上调节E3结合酶活性.
- 这种机制提供了一个反系统,以调节基于细胞内二水平的吸收.
- 表明小分子可能是其他依赖于无素的蛋白质降解途径的一般调节者.
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