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首页> 外文期刊>Molecular and Cellular Biology >The ability of C/EBP beta but not C/EBP alpha to synergize with an Sp1 protein is specified by the leucine zipper and activation domain.
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The ability of C/EBP beta but not C/EBP alpha to synergize with an Sp1 protein is specified by the leucine zipper and activation domain.

机译：C / EBP beta而非C / EBP alpha与Sp1蛋白协同作用的能力由亮氨酸拉链和激活域确定。

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The rat CYP2D5 P-450 gene is activated in the liver during postnatal development. We previously showed that liver-specific transcription of the CYP2D5 gene is dictated by a proximal promoter element, termed 2D5, that is composed of a binding site for Sp1 or a related factor, and an adjacent cryptic C/EBP (CCAAT/enhancer-binding protein) site. Despite the fact that both C/EBP alpha and C/EBP beta are expressed abundantly in liver, only C/EBP beta is capable of stimulating the 2D5 promoter in HepG2 hepatocarcinoma cells. In addition, activation of the 2D5 promoter by C/EBP beta is completely dependent on the presence of the Sp1 site. Domain switch experiments reveal that C/EBP beta proteins containing either the leucine zipper or the activation domain of C/EBP alpha are unable to stimulate the 2D5 promoter yet are fully capable of transactivating an artificial promoter bearing a high-affinity C/EBP site. Thus, the leucine zipper and the activation domain of C/EBP beta are absolutely required to support transactivation of the 2D5 promoter. Using Drosophila cells that lack endogenous Sp1 activity, we show that the serine/threonine- and glutamine-rich activation domains A and B of Sp1 are required for efficient cooperatively with C/EBP beta. Furthermore, analysis of c/ebp beta-deficient mice shows that mutant animals are defective in expression of a murine CYP2D5 homolog in hepatic cells, confirming the selective ability of C/EBP beta to activate this liver-specific P-450 gene in vivo. Our findings illustrate that two members of a transcription factor family can achieve distinct target gene specificities through differential interactions with a cooperating Sp1 protein.
机译：大鼠CYP2D5 P-450基因在产后发育期间在肝脏中被激活。先前我们曾证明CYP2D5基因的肝脏特异性转录是由一个近端启动子元件（称为2D5）决定的，该元件由Sp1或相关因子的结合位点以及一个相邻的C / EBP（CCAAT /增强子结合）蛋白）位点。尽管C / EBP alpha和C / EBP beta均在肝脏中大量表达，但只有C / EBP beta能够刺激HepG2肝癌细胞中的2D5启动子。另外，C / EBP beta对2D5启动子的激活完全取决于Sp1位点的存在。域转换实验表明，含有亮氨酸拉链或C / EBPα激活域的C / EBPβ蛋白无法刺激2D5启动子，但完全能够激活具有高亲和力C / EBP位点的人工启动子。因此，绝对需要亮氨酸拉链和C / EBP beta的激活域来支持2D5启动子的反式激活。使用缺乏内源性Sp1活性的果蝇细胞，我们显示Sp1富含丝氨酸/苏氨酸和谷氨酰胺的激活域A和B是与C / EBP beta有效协作所必需的。此外，对c / ebpβ缺陷小鼠的分析表明，突变动物在肝细胞中的鼠CYP2D5同源物表达方面存在缺陷，证实了C / EBPβ在体内激活该肝特异性P-450基因的选择性能力。我们的发现表明，转录因子家族的两个成员可以通过与协同作用的Sp1蛋白的不同相互作用实现不同的靶基因特异性。

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