缺乏其激活域的Jun转录因子的转化抑制活性
A Lloyd1, N Yancheva, B Wasylyk
1LGME-CNRS, U184-INSERM, Institut de Chimie Biologique, Faculté de Medecine, Strasbourg, France.
Nature
|August 15, 1991
概括
蛋白c-Jun对于Ras介导的细胞转化是必不可少的. 一种主导负的Jun突变抑制Ras转化并恢复正常的细胞生长,作为一种抗瘤基因.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞转化 细胞转化
背景情况:
- 蛋白c-Jun与Ras介导的细胞转化有关.
- c-Jun合成和转录因子活性都由Ras.上调调节.
- c-Jun和Ras在转换试验中合作,建议不同的但相互作用的途径.
研究的目的:
- 调查c-Jun的必要性,可能与相互作用的因素,用于Ras介导的细胞转化.
- 描述一个主导负的Jun突变对转录和细胞转化的影响.
- 探索Jun突变体作为抗瘤基因的潜力.
主要方法:
- 使用了缺少激活域的主导负变异转录因子 (Jun变异).
- 评估了各种瘤蛋白和瘤促进剂 (TPA) 抑制转录刺激的作用.
- 检查了Jun结合动机的抑制特异性,与NF-kappa B/Rel动机激活形成对比.
- 评估了Jun突变体在Ras转型细胞中的抗瘤活性,评估了生长特征和瘤性.
主要成果:
- 主导阴性Jun突变特异地阻断了由Ras和其他coproteins介导的转录刺激.
- 抑制是Jun结合动机的特征,使NF-kappa B/Rel激活不受影响.
- 突变基因在Ras转型细胞中起到抗瘤基因的作用,诱导向非转型表型的逆转.
- 复原细胞表现出恢复的定和密度依赖的生长,以及体内瘤发生率降低.
结论:
- c-Jun,可能与相互作用的合作伙伴,是Ras介导的细胞转化所必需的.
- 主导阴性Jun突变可以作为抗瘤基因,逆转瘤原性表型.
- 这种方法提供了一种方法来研究转录因子在信号传导和转换中的作用.
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