在体内依赖于乌比奎丁的c-Jun降解是由三角域介导的
M Treier1, L M Staszewski, D Bohmann
1European Molecular Biology Laboratory, Differentiation Programme, Heidelberg, Federal Republic of Germany.
Cell
|September 9, 1994
概括
这种依赖于ubiquitin的蛋白质分解系统针对c-Jun进行分解,但不针对v-Jun. 在c-Jun中的三角形域调解了这种无处不在和降解,这表明了新的瘤发生路径.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 这种依赖于乌比基的蛋白质分解系统调节了蛋白质的循环.
- c-Jun是一种转录因子,参与细胞增殖和分化.
- v-Jun 是一种来自c-Jun的病毒性蛋白.
研究的目的:
- 为了研究在c-Jun分解中依赖于乌比奎的蛋白质分解系统的作用.
- 为了比较c-Jun和v-Jun的降解路径.
- 确定c-Jun和v-Jun稳定性的分子决定因素.
主要方法:
- 在体外无化测试.
- 在体内测试使用分子标记的乌比奎和c-Jun.
- 在c-Jun和v-Jun的局部定向突变发生.
- 蛋白质半衰期测量 蛋白质半衰期测量
- 功能转移c-Jun序列到一个记者蛋白 (β-galactosidase).
主要成果:
- c-Jun是高效的多元化,而v-Jun不是.
- 与c-Jun相比,v-Jun的半衰期更长.
- 在c-Jun中,delta域 (27个氨基酸) 负责其无处不在和降解.
- 在v-Jun中delta域的删除使得它具有对无处不在和降解的抗性.
- 当被转移到其他蛋白质时,三角域充当cis作用的泛化和降解信号.
结论:
- c-Jun的三角形域是其依赖于无处不在的降解的关键决定因素.
- 脱离乌比基介导的蛋白解有助于v-Jun.的致癌潜力.
- 这项研究揭示了一种新的机制,将蛋白质降解途径与瘤发生联系起来.
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