Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells
Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells
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DOI：
10.1073/pnas.1932773100
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发表时间：
2003-10-14
影响因子：
11.1
通讯作者：
Labow, MA
中科院分区：
文献类型：
--
作者：
Iourgenko, V;Zhang, WJ;Labow, MA
本报告描述了一种无偏的方法，用于系统地确定哺乳动物细胞中的基因功能。总共测试了20,704个预测的人类全长CDNA，以诱导IL-8启动子。鉴定出许多基因，包括细胞因子，受体，衔接子，激酶和转录因子的基因，这些基因通过已知的调节位点诱导IL-8启动子。还确定了通过AP-1与未识别的cAMP反应元件（CRE）状位点进行合作相互作用的蛋白质。鉴定出一种被称为调节的cAMP反应元件结合蛋白（CREB）（TORC1）的蛋白质，该蛋白通过变体CRE和共识CRE位点激活了表达。 TORC1有效诱导已知的CREB1靶基因，结合了CREB1，并通过有效的转录激活域激活了表达。还鉴定出功能性果蝇基因。因此，TORC代表了一个高度保守的CREB共激活因子家族，可以控制CRE介导的反应的效力和特异性。
This report describes an unbiased method for systematically determining gene function in mammalian cells. A total of 20,704 predicted human full-length cDNAs were tested for induction of the IL-8 promoter. A number of genes, including those for cytokines, receptors, adapters, kinases, and transcription factors, were identified that induced the IL-8 promoter through known regulatory sites. Proteins that acted through a cooperative interaction between an AP-1 and an unrecognized cAMP response element (CRE)-like site were also identified. A protein, termed transducer of regulated cAMP response element-binding protein (CREB) (TORC1), was identified that activated expression through the variant CRE and consensus CRE sites. TORC1 potently induced known CREB1 target genes, bound CREB1, and activated expression through a potent transcription activation domain. A functional Drosophila TORC gene was also identified. Thus, TORCs represent a family of highly conserved CREB coactivators that may control the potency and specificity of CRE-mediated responses.