Páez J G, Recio J A, Rouzaut A, Notario V
Laboratory of Experimental Carcinogenesis, Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
Int J Oncol. 2001 Dec;19(6):1249-54. doi: 10.3892/ijo.19.6.1249.
PCPH was initially defined as a proto-oncogene on the basis of its frequent detection as an activated oncogene in tumorigenic Syrian hamster embryo fibroblast cell lines converted to the neoplastic state by a single treatment with the carcinogen 3-methylcholanthrene (MC). Further studies identified the translation product of the PCPH gene as a ribonucleotide-binding protein with special affinity for ribonucleoside diphosphates. Later, we showed that the PCPH protein was homologous to the product of the yeast GDA1 gene and demonstrated that it had intrinsic guanosine diphosphatase activity, although it did not complement the disrupted phenotype when expressed in gda1 null Saccharomyces cerevisiae strains. These results indicated that the primary function of PCPH was unlikely to be related to the ribonucleotide recycling function that its yeast counterpart performs in the Golgi during the process of protein glycosylation. However, taken together, our data strongly suggested that the normal cellular function of PCPH was related to ribonucleotide metabolism. We now report that PCPH is structurally and functionally identical to the mammalian ectonucleoside triphosphate diphosphohydrolase CD39L4 (ENTPD5), recently described as a member of the lymphoid activation antigen (
PCPH最初被定义为一种原癌基因，这是基于它在经致癌物3-甲基胆蒽（MC）单次处理后转化为肿瘤状态的致瘤叙利亚仓鼠胚胎成纤维细胞系中，经常作为一种激活的癌基因被检测到。进一步的研究确定PCPH基因的翻译产物是一种对核糖核苷二磷酸具有特殊亲和力的核糖核苷酸结合蛋白。后来，我们发现PCPH蛋白与酵母GDA1基因的产物同源，并证明它具有内在的鸟苷二磷酸酶活性，尽管当它在gda1缺失的酿酒酵母菌株中表达时，不能补充其破坏的表型。这些结果表明，PCPH的主要功能不太可能与其酵母对应物在蛋白质糖基化过程中在高尔基体中执行的核糖核苷酸循环功能有关。然而，综合来看，我们的数据强烈表明PCPH的正常细胞功能与核糖核苷酸代谢有关。我们现在报告，PCPH在结构和功能上与哺乳动物胞外核苷三磷酸二磷酸水解酶CD39L4（ENTPD5）相同，CD39L4最近被描述为淋巴激活抗原（<分化簇>）CD39蛋白家族的一员。这些结果可能有助于确定PCPH原癌基因产物的正常细胞功能及其在致癌过程中肿瘤发生中的作用。
