酸化依赖于SCFFbw7 ubiquitin结合酶的环林E的无化
D M Koepp1, L K Schaefer, X Ye
1Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, 77030, USA.
Science (New York, N.Y.)
|September 5, 2001
概括
这项研究确定SCFFbw7是控制环林E蛋白水平的全域化酶. 这种机制在各个物种中得到保护,确保了细胞周期的正常进展.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 循环E/Cdk2复合体驱动G1到S阶段的过渡.
- 严格调节循环E蛋白水平对于细胞周期控制至关重要.
- 乌比奎介导的蛋白质分解是蛋白质降解的关键机制.
研究的目的:
- 为了识别负责Cyclin E ubiquitination的乌比基因酶.
- 为了研究这种结合酶在不同物种的功能性保存.
- 了解SCFFbw7在Cyclin E蛋白稳定性和细胞循环调节中的作用.
主要方法:
- 通过生物化学测试识别乌比基酸酶.
- 在实验室使用SCFFbw7和Cyclin E.进行的ubiquitination测定.
- 在体内研究涉及人类,和酵母细胞的基因枯竭.
- 分析蛋白质的积累和稳定性.
主要成果:
- SCFFbw7被确定为Cyclin E.的特定无素酶.
- Fbw7与酸化的环素E.特别相关.
- 在体外,SCFFbw7催化了环林E的泛化.
- 耗尽Fbw7导致循环蛋白E的积累和稳定在体内.
- 在酵母,和哺乳动物中证明Fbw7在调节环林E稳定性的功能性保护.
结论:
- SCFFbw7是主要的E3泛基因化酶,针对Cyclin E进行降解.
- 对于Cyclin E而言,Fbw7介导的降解途径在进化过程中得到了保留.
- 在酵母中发现的结果表明,SCF E3酶对循环环E稳定性的组合控制.
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