通过LIM-only蛋白ACT对CREM和CREB的CBP独立激活
G M Fimia1, D De Cesare, P Sassone-Corsi
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-ULP, Illkirch, Strasbourg, France.
Nature
|March 23, 1999
概括
研究人员发现了ACT,这是一种新型蛋白质,可以激活丸中的CREM (cAMP反应元件调节器) 转录. 这种激活剂绕过了传统的酸化和CBP相互作用,这表明了男性生殖细胞中基因调节的新途径.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 生殖生物学 生殖生物学
背景情况:
- 通过CREB (cAMP响应元素结合蛋白) 和CREM (cAMP响应元素调节器) 进行转录激活通常需要酸化和同活性剂CBP相互作用.
- 在介质后阶段,CREM对于男性生殖细胞的基因表达至关重要.
研究的目的:
- 确定参与CREM介导的丸转录激活的新型蛋白质.
- 描述一个新发现的丸特异性激活剂的功能和机制.
主要方法:
- 采用双混合屏幕,从丸cDNA库中分离与CREM相互作用的蛋白质.
- 用酵母和哺乳动物细胞的功能测试来评估已识别的蛋白质对CREM转录活性的影响.
- 新型蛋白质的表达模式以特定的组织和发育方式进行分析.
主要成果:
- 分离了编码LIM-only蛋白的丸衍生cDNA,称为ACT (丸中的CREM激活器).
- ACT与CREM特别关联,并以组织和发育调节的方式与CREM协调表达.
- ACT强烈刺激CREM转录活性,绕过了对Ser 117酸化和CBP相互作用的需要.
结论:
- ACT代表了由CREM和CREB进行转录激活的新途径,独立于正规机制.
- ACT可能构成一种新的组织特异性协活性剂类别,涉及不同的细胞分化程序,特别是在男性生殖细胞发育过程中.
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