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首页> 外文期刊>Molecular and Cellular Biology >Transcriptional activation of the fra-1 gene by AP-1 is mediated by regulatory sequences in the first intron.
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Transcriptional activation of the fra-1 gene by AP-1 is mediated by regulatory sequences in the first intron.

机译：AP-1对fra-1基因的转录激活是由第一个内含子中的调控序列介导的。

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摘要

Constitutive expression of c-Fos, FosB, Fra-1, or c-Jun in rat fibroblasts leads to up-regulation of the immediate-early gene fra-1. Using the posttranslational FosER induction system, we demonstrate that this AP-1-dependent stimulation of fra-1 expression is rapid, depends on a functional DNA-binding domain of FosER, and is a general phenomenon observed in different cell types. In vitro mutagenesis and functional analysis of the rat fra-1 gene in stably transfected Rat-1A-FosER fibroblasts indicated that basal and AP-1-regulated expression of the fra-1 gene depends on regulatory sequences in the first intron which comprise a consensus AP-1 site and two AP-1-like elements. We have also investigated the transactivating and transforming properties of the Fra-1 protein to address the significance of fra-1 up-regulation. The entire Fra-1 protein fused to the DNA-binding domain of Ga14 is shown to lack any transactivation function, and yet it possesses oncogenic potential, as overexpression of Fra-1 in established rat fibroblasts results in anchorage-independent growth in vitro and tumor development in athymic mice, fra-1 is therefore not only induced by members of the Fos family, but its gene product may also contribute to cellular transformation by these proteins. Together, these data identify fra-1 as a unique member of the fos gene family which is under positive control by AP-1 activity.
机译：大鼠成纤维细胞中c-Fos，FosB，Fra-1或c-Jun的组成型表达导致即早基因fra-1的上调。使用翻译后的FosER诱导系统，我们证明了fra-1表达的这种AP-1依赖性刺激是快速的，取决于FosER的功能性DNA结合域，并且是在不同细胞类型中观察到的普遍现象。在稳定转染的Rat-1A-FosER成纤维细胞中大鼠fra-1基因的体外诱变和功能分析表明，fra-1基因的基础表达和AP-1调控取决于第一内含子的调控序列AP-1站点和两个类似于AP-1的元素。我们还研究了Fra-1蛋白的反式激活和转化特性，以解决fra-1上调的重要性。与Ga14的DNA结合结构域融合的整个Fra-1蛋白显示没有任何反式激活功能，但它具有致癌潜力，因为已建立的大鼠成纤维细胞中Fra-1的过度表达导致体外和肿瘤的锚定非依赖性生长因此，fra-1在无胸腺小鼠的体内发育中不仅受到Fos家族成员的诱导，而且其基因产物也可能通过这些蛋白质促进细胞转化。这些数据一起将fra-1鉴定为fos基因家族的独特成员，该家族受AP-1活性的正调控。

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