人类原型瘤基因c-jun编码一种具有转录因子AP-1结构和功能性质的DNA结合蛋白
1Howard Hughes Medical Institute, Department of Biochemistry, University of California, Berkeley, CA 94720.
概括
人类原型瘤基因c-jun编码一种与转录因子AP-1相似的DNA序列结合的蛋白质. 这一发现将c-jun与基因调节和癌症发展联系起来.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 基因规则 基因规则
背景情况:
- 核瘤基因产品可以改变基因调节,可能导致癌症.
- 核蛋白作用的精确机制尚未完全理解.
- 瘤基因v-jun与酵母转录因子GCN4的DNA结合域具有同质性,GCN4可以识别类似的DNA序列作为AP-1.
研究的目的:
- 研究人类原瘤基因c-jun与增强剂结合蛋白AP-1之间的关系.
- 为了确定c-jun产品是否与DNA序列直接相互作用以调节基因表达.
主要方法:
- 人类原瘤基因的分离和克隆 c-jun.
- 克隆的c-jun的细菌表达产生蛋白质.
- 针对v-jun的抗体生成,用于与人类AP-1进行交叉反应性测试.
- 部分氨基酸测序纯化的AP-1.
主要成果:
- 推断出的c-jun的氨基酸序列显示了与v-jun的80%以上的相同性.
- 细菌表达c-jun产生了一种具有与AP-1相同的DNA结合特性的蛋白质.
- 针对v-jun的抗体与人类AP-1特别反应.
- AP-1的部分测序揭示了与c-jun蛋白共享的三性.
结论:
- 结构和功能上的相似性强烈地表明,AP-1被c-jun. encode编码.
- 这种c-jun原型瘤基因产物直接结合特定的DNA序列来调节基因表达.
- 这一发现使得能够识别由c-jun控制的,影响细胞生长和瘤的基因.
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