氨酸重复和相邻的DNA结合域介导功能cFos-cJun异构体的形成
1Howard Hughes Medical Institute, Department of Biochemistry, University of California, Berkeley 94720.
概括
俊综合体将癌症与基因调节联系在一起. 和蛋白形成异构体,使得DNA结合并推进对原型基因功能的理解.
科学领域:
- 分子生物学分子生物学
- 瘤发生的发生因子.
- 转录条例 转录条例 转录条例
背景情况:
- 增强剂结合因子的AP-1家族对于将瘤发生与转录调节联系起来至关重要.
- 细胞Fos (cFos) 和细胞Jun (cJun) 蛋白质构成AP-1家族中的一个关键复合体.
研究的目的:
- 研究Fos和Jun蛋白质的蛋白质-蛋白质相互作用和DNA结合特性.
- 阐明了cFos-cJun复合体的形成和功能背后的分子机制.
主要方法:
- 在cFos和cJun蛋白质的体外合成和共翻译.
- 对同质和异质复合物的DNA结合能力的分析.
- 针对cFos的突变发生,以确定蛋白质相互作用和DNA结合的关键域.
主要成果:
- 同位体cJun结合AP-1位点,但cFos没有.
- 同转化cFos和cJun形成一个稳定的异构体,具有AP-1/cJun的DNA结合特性.
- 俊B和vJun也与cFos.形成了DNA结合复合体.
- 在cFos中的leucine重复对于绑定cJun至关重要,与leucine拉链模型一致.
- 对于cFos-cJun异构体中DNA结合而言,需要在cFos中的一个新域,与白重复区分开来.
结论:
- 氨酸重复介导异质蛋白质复合体的形成.
- 实验证据支持白重复在蛋白质与蛋白质相互作用中的作用.
- 这项研究增强了对涉及Fos和Jun等原型瘤基因产品的分子机制的理解.
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