Expression pattern and preliminary functional analysis of human CREB4 gene.

Yong-Juan Gao, Gen-Tao Cao, Gang Yin, Xin Wang, Chao-Neng Ji, Shao-Hua Gu, Xiao-Hua Ni
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Abstract

cAMP response element-binding (CREB) proteins are a family of mammalian transcription activators that mediate cAMP and calcium-dependent gene expression through the cAMP response element (CRE). CREB4 is a novel member of the human CREB family. RT-PCR showed CREB4 transcripts were found in lung carcinoma LX-1, colon adenocarcinoma CX-1, prastatic adenocarcinoma PC-3, colon carcinoma G1-112, and pancreatic adenocarcinoma G1-103. Constructing CREB4 and CREB(215-395aa) fusion protein with the entire prokaryotic LexA protein respectively disclosed that CREB4 protein functioned as a transcription activator and its N-terminal accounted for the activation ability. Furthermore,a fusion protein of GFP and full-length CREB4 was localized in cytoplasm,whereas the fusion protein of GFP and a deletion mutant lacking the C-terminal putative transmembrane domain was translocated in nucleus. Our results suggested that putative transmembrane domain of CREB4 protein was associated with modulation of its function for the transcriptional activation.

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人CREB4基因表达模式及初步功能分析。
cAMP反应元件结合蛋白(CREB)是一个哺乳动物转录激活因子家族,通过cAMP反应元件(CRE)介导cAMP和钙依赖性基因的表达。CREB4是人类CREB家族的新成员。RT-PCR结果显示,在肺癌LX-1、结肠癌CX-1、前列腺癌PC-3、结肠癌G1-112、胰腺腺癌G1-103中均发现了CREB4转录物。分别与整个原核生物LexA蛋白构建CREB4和CREB(215-395aa)融合蛋白,发现CREB4蛋白具有转录激活因子的功能,其n端具有激活能力。此外,GFP与全长CREB4的融合蛋白定位在细胞质中,而GFP与缺乏c端跨膜结构域的缺失突变体的融合蛋白在细胞核中易位。我们的研究结果表明,CREB4蛋白的跨膜结构域与其转录激活功能的调节有关。
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