Hartl M, Bister K
Institute of Biochemistry, University of Innsbruck, Austria.
Oncogene. 1998 Dec 3;17(22):2901-13. doi: 10.1038/sj.onc.1202219.
The BKJ gene was originally identified based on its specific transcriptional activation in jun-transformed avian fibroblasts. We now show that BKJ is a direct transcriptional target of the AP-1 transcription factor components Jun and Fos. The complete structural organization of the quail BKJ gene was determined by nucleotide sequence analysis and transcriptional mapping. The gene contains three exons with the coding region confined to the third exon. A major mRNA species of 0.8 kb and a minor one of 1.3 kb are produced by variable usage of two transcriptional initiation sites. The BKJ promoter region contains two authentic AP-1 binding sites. By transactivation of reporter gene constructs and direct binding of Jun recombinant protein, the proximal AP-1 element was shown to be essential for BKJ promoter activation. Using polyclonal antiserum directed against recombinant BKJ protein, the activation of BKJ in jun-transformed avian fibroblasts was also demonstrated at the protein level. BKJ is a novel gene related to the avian beta-keratin gene family whose members display highly specific expression patterns during embryogenesis and epidermal development. Activation of BKJ in fibroblasts by retroviral or deregulated cellular jun or fos alleles may contribute to cell transformation.
BKJ基因最初是根据其在jun转化的禽成纤维细胞中的特异性转录激活而被鉴定出来的。我们现在表明,BKJ是AP-1转录因子成分Jun和Fos的直接转录靶点。通过核苷酸序列分析和转录图谱确定了鹌鹑BKJ基因的完整结构组织。该基因包含三个外显子,编码区局限于第三个外显子。通过可变使用两个转录起始位点产生了一种主要的0.8 kb mRNA物种和一种次要的1.3 kb mRNA物种。BKJ启动子区域包含两个真实的AP-1结合位点。通过报告基因构建体的反式激活和Jun重组蛋白的直接结合,近端AP-1元件被证明对BKJ启动子激活至关重要。使用针对重组BKJ蛋白的多克隆抗血清,在蛋白水平上也证明了BKJ在jun转化的禽成纤维细胞中的激活。BKJ是一个与禽β-角蛋白基因家族相关的新基因,其成员在胚胎发生和表皮发育过程中表现出高度特异性的表达模式。逆转录病毒或失调的细胞jun或fos等位基因在成纤维细胞中激活BKJ可能有助于细胞转化。