在转录因子CREB中对双部分激活子域的表征
K K Yamamoto1, G A Gonzalez, P Menzel
1Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
Cell
|February 23, 1990
概括
研究人员确定了一个CREBα区域,该区域对转录至关重要. 这一区域,一个两螺旋,与激酶A相互作用,增强了真核细胞中CREB蛋白活性.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 蛋白质结构和功能 蛋白质结构和功能
背景情况:
- CREB (cAMP反应元素结合蛋白) 是一种转录因子,对基因表达至关重要.
- 了解CREB的调节机制是解读细胞反应的关键.
研究的目的:
- 描述CREB中一种新的转激活区域,称为alpha.
- 为了研究α区域,激酶A酸化和转录活性之间的相互作用.
- 阐明CREB活动的结构基础.
主要方法:
- 在体外突变发生的实验来评估CREB活性.
- 在合成α上进行循环二重化谱学.
- 在真核细胞中分析CREB和三角CREB的表达.
主要成果:
- 在CREB中确定了一个转激活区域,alpha,它与激酶A酸化合作,刺激转录.
- 阿尔法区域被一个替代的外原编码,在相关的三角形CREBcDNA中不存在.
- 在真核细胞中,CREB的活性比delta CREB高10倍.
- 循环二重化和突变基因的数据表明,阿尔法区域包含一个关键的两方形阿尔法螺旋环.
结论:
- CREB的α区域,很可能是两性α螺旋,对于CREB的转录活动至关重要.
- 激酶A酸化可能通过改变聚合酶II复合体内的α区域的结构和蛋白质相互作用来增强CREB活性.
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