Van Hoof C, Aly M S, Garcia A, Cayla X, Cassiman J J, Merlevede W, Goris J
Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Belgium.
Genomics. 1995 Jul 20;28(2):261-72. doi: 10.1006/geno.1995.1140.
The PTPA gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. PTPA, cloned from human genomic libraries, is encoded by one single-copy gene, composed of 10 exons and 9 introns with a total length of about 60 kb. The transcription start site was determined, and the 5' flanking sequence was analyzed for its potential as a promotor. This region lacks a TATA sequence in the appropriate position relative to the transcription start, is very GC-rich, and contains upstream of the transcription start four Sp1 sites, a feature common to many TATA-less promotors. Based on the homology with DNA binding consensus sequences of transcription factors, we identified in this promotor region several putative DNA binding sites for transcription factors, such as NF-kappa B, Myb, Ets-1, Myc, and ATF. Transfection experiments with a construct containing the PTPA promotor region inserted 5' of a luciferase reporter gene revealed that the 5' flanking sequence of the PTPA gene indeed displayed promotor activity that seems to be cell-line dependent. By fluorescence in situ hybridization and G-banding, the PTPA gene was localized to the 9q34 region. The PTPA gene is positioned centromeric of c-abl in a region embracing several genes implicated in oncogenesis.
PTPA基因编码蛋白磷酸酶2A二聚体形式的一种特定磷酸酪氨酸磷酸酶激活剂。从人类基因组文库中克隆得到的PTPA由一个单拷贝基因编码,该基因由10个外显子和9个内含子组成,全长约60 kb。确定了转录起始位点,并对5'侧翼序列作为启动子的潜力进行了分析。该区域在相对于转录起始的适当位置缺乏TATA序列,富含GC,并且在转录起始上游包含四个Sp1位点,这是许多无TATA启动子共有的特征。基于与转录因子DNA结合共有序列的同源性,我们在该启动子区域鉴定了几个转录因子的假定DNA结合位点,如NF-κB、Myb、Ets-1、Myc和ATF。用含有插入荧光素酶报告基因5'端的PTPA启动子区域的构建体进行转染实验表明,PTPA基因的5'侧翼序列确实表现出启动子活性,且这种活性似乎依赖于细胞系。通过荧光原位杂交和G带分析,PTPA基因定位于9q34区域。PTPA基因位于c-abl的着丝粒一侧,该区域包含几个与肿瘤发生相关的基因。