CYCLIC-AMP - RESPONSIVE DNA-BINDING PROTEIN - STRUCTURE BASED ON A CLONED PLACENTAL CDNA
CYCLIC-AMP - RESPONSIVE DNA-BINDING PROTEIN - STRUCTURE BASED ON A CLONED PLACENTAL CDNA
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DOI：
10.1126/science.2974179
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发表时间：
1988-12-09
期刊：
影响因子：
56.9
通讯作者：
HABENER, JF
中科院分区：
文献类型：
--
作者：
HOEFFLER, JP;MEYER, TE;HABENER, JF
环磷酸腺苷(CAMP)是细胞内的第二信使，可激活多种细胞基因的转录。回文共识DNA序列TGACGTCA作为cAMP反应转录增强子(CRE)发挥作用。Cre结合胎盘JEG-3细胞中38kD的细胞蛋白。以Cre序列作为放射性探针，筛选胎盘.lambda.gt11文库中特异性Cre结合蛋白的表达。克隆了一个编码326个氨基酸的蛋白的cDNA，该蛋白具有Cre结合蛋白(CREB)的结合特性。该蛋白质含有COOH末端碱性区域，毗邻一个类似于被认为参与DNA结合的亮氨酸拉链序列的序列，并在其他几种DNA相关转录蛋白中参与蛋白质-蛋白质接触，包括c-myc、c-fos和c-jun癌基因和GCN4的产物。CREB蛋白还含有一个NH2末端的酸性区域，被认为是一个潜在的转录激活结构域。CREB的DNA结合域在结构上与佛波酯反应的c-jun蛋白和酵母转录因子Gcn4中的相应结构域相似。
Cyclic AMP (cAMP) is an intracellular second messenger that activates transcription of many cellular genes. A palindromic consensus DNA sequence, TGACGTCA, functions as a cAMP-responsive transcriptional enhancer (CRE). The CRE binds a cellular protein of 38 kD in placental JEG-3 cells. A placental .lambda.gt11 library was screened for expression of specific CRE-binding proteins with the CRE sequence as a radioactive probe. A cDNA encoding a protein of 326 amino acids with the binding properties of a specific CRE-binding protein (CREB) was isolated. The protein contains of COOH-terminal basic region adjacent to a sequence similar to the "leucine zipper" sequence believed to be involved in DNA binding and in protein-protein contacts in several other DNA-associated transcriptional proteins including the products of the c-myc, c-fos, and c-jun oncogenes and GCN4. The CREB protein also contains an NH2-terminal acidic region proposed to be a potential transcriptional activation domain. The putative DNA-binding domain of CREB is structurally similar to the corresponding domains in the phorbol ester-responsive c-jun protein and the yeast transcription factor GCN4.