首页> 外文期刊>Molecular and Cellular Biology >Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cellular factor.
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Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cellular factor.

机译:Luman是CREB ​​/ ATF家族的新成员,与单纯疱疹病毒VP16相关的宿主细胞因子结合。

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The human host cell factor (HCF) is expressed in a variety of adult and fetal tissues, and its gene is conserved in animals as diverse as mammals and insects. However, its only known function is to stabilize the herpes simplex virus virion transactivator VP16 in a complex with the cellular POU domain protein Oct-1 and cis-acting regulatory elements in promoters of immediate-early viral genes. To identify a cellular function for HCF, we used the yeast two-hybrid system to identify a cellular ligand for HCF. This protein, Luman, appears to be a cyclic AMP response element (CRE)-binding protein/activating transcription factor 1 protein of the basic leucine zipper superfamily. It binds CREs in vitro and activates CRE-containing promoters when transfected into COS7 cells. This activation of transcription was synergistically enhanced by the presence of CCAAT/enhancer-binding protein elements and inhibited by AP-1 elements in the promoter. In addition to a basic DNA binding domain, Luman possesses an unusually long leucine zipper and an acidic amino-terminal activation domain. These features in Luman are also present in what appear to be homologs in the mouse, Drosophila melanogaster, and Caenorhabditis elegans. Luman and VP16 appear to have similar mechanisms for binding HCF, as in vitro each competitively inhibited the binding of the other to HCF. In transfected cells, however, while VP16 strongly inhibited the ability of GAL-Luman to activate transcription from a GAL4 upstream activation sequence-containing promoter, Luman was unable to inhibit the activity of GAL-VP16. Luman appears to be a ubiquitous transcription factor, and its mRNA was detected in all human adult and fetal tissues examined. The possible role of HCF in regulating the function of this ubiquitous transcription factor is discussed.
机译:人宿主细胞因子(HCF)在各种成年和胎儿组织中表达,其基因在哺乳动物和昆虫等多种动物中均得到保守。然而,其唯一已知的功能是将单纯疱疹病毒病毒粒子反式激活因子VP16与细胞POU结构域蛋白Oct-1和立即早期病毒基因启动子中的顺式作用调节元件复合在一起。为了鉴定HCF的细胞功能,我们使用酵母双杂交系统鉴定HCF的细胞配体。该蛋白Luman似乎是碱性亮氨酸拉链超家族的环状AMP反应元件(CRE)结合蛋白/激活转录因子1蛋白。它在体外结合CRE,并在转染到COS7细胞后激活含CRE的启动子。 CCAAT /增强子结合蛋白元件的存在可协同增强转录的激活,启动子中的AP-1元件可抑制转录的激活。除了基本的DNA结合结构域外,Luman还具有一个异常长的亮氨酸拉链和一个酸性氨基末端激活结构域。 Luman中的这些特征也存在于小鼠,果蝇和秀丽隐杆线虫的同系物中。 Luman和VP16似乎具有类似的结合HCF的机制,因为在体外,每个竞争性抑制了彼此与HCF的结合。然而,在转染的细胞中,虽然VP16强烈抑制GAL-Luman激活含GAL4上游激活序列的启动子转录的能力,但Luman无法抑制GAL-VP16的活性。 Luman似乎是一种普遍存在的转录因子,并且在所有检查的成人和胎儿组织中均检测到其mRNA。讨论了HCF在调节该普遍存在的转录因子功能中的可能作用。

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