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首页> 外文期刊>The Biochemical Journal >cAMP-response-element-binding-protein binding protein (CBP) and p300 are transcriptional co-activators of early growth response factor-1 (Egr-1)
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cAMP-response-element-binding-protein binding protein (CBP) and p300 are transcriptional co-activators of early growth response factor-1 (Egr-1)

机译：cAMP反应元件结合蛋白结合蛋白（CBP）和p300是早期生长反应因子1（Egr-1）的转录共激活因子

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摘要

Egr-1 (early-growth response factor-1) is a sequence-specific transcription factor that plays a regulatory role in the expression of many genes important for cell growth, development and the pathogenesis of disease. The transcriptional co-activators CBP (cAMP-response-element-binding-protein-binding protein) and p300 interact with sequence-specific transcription factors as well as components of the basal transcription machinery to facilitate RNA polymerase II recruitment and transcriptional initiation. Here we demonstrate a unique way in which Egr-1 physically and functionally interacts with CBP/p300 to modulate gene transcription. CBP/p300 potentiated Egr-1 mediated expression of 5-lipoxygenase (5-LO) promoter-reporter constructs, and the degree of trans-activation was proportional to the number of Egr-1 consensus binding sites present in wild-type and naturally occurring mutants of the 5-LO promoter. The N- and C-terminal domains of CBP interact with the transcriptional activation domain of Egr-1, as demonstrated by a mammalian two-hybrid assay. Direct protein-protein interactions between CBP/p300 and Egr-1 were demonstrated by glutathione S-transferase fusion-protein binding and co-immunoprecipitation/Western-blot studies. These data suggest that CBP and p300 act as transcriptional co-activators for Egr-1-mediated gene expression and that variations between individuals in such co-activation could serve as a genetic basis for variability in gene expression. [References: 40]
机译：Egr-1（早期生长反应因子-1）是一种序列特异性转录因子，在许多对细胞生长，发育和疾病发病机理重要的基因的表达中起调节作用。转录共激活因子CBP（cAMP-反应-元素-结合蛋白-结合蛋白）和p300与序列特异性转录因子以及基础转录机制的成分相互作用，以促进RNA聚合酶II的募集和转录起始。在这里，我们演示了Egr-1在物理和功能上与CBP / p300相互作用以调节基因转录的独特方式。 CBP / p300增强了Egr-1介导的5-脂氧合酶（5-LO）启动子-报告子构建体的表达，反式激活程度与野生型和天然存在的Egr-1共有结合位点的数量成正比5-LO启动子的突变体。 CBP的N和C末端结构域与Egr-1的转录激活结构域相互作用，如哺乳动物两杂交试验所证明的。谷胱甘肽S-转移酶融合蛋白结合和免疫共沉淀/蛋白质印迹研究证明了CBP / p300和Egr-1之间的直接蛋白相互作用。这些数据表明，CBP和p300充当Egr-1介导的基因表达的转录共激活因子，并且这种共激活过程中个体之间的变异可以作为基因表达变异的遗传基础。 [参考：40]

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