Identity between the PCPH proto-oncogene and the CD39L4 (ENTPD5) ectonucleoside triphosphate diphosphohydrolase gene.
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 (<cluster of differentiation>) CD39 protein family. These results may help to establish the normal cellular function of the PCPH proto-oncogene product and its role in neoplastic development during carcinogenesis.
Páez
J G
JG
Laboratory of Experimental Carcinogenesis, Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
Recio
J A
JA
Rouzaut
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Notario
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D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics*; D000255:Adenosine Triphosphate / Q000378:metabolism; D001483:Base Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D014176:Protein Biosynthesis; D000090063:Proto-Oncogene Mas; D011755:Pyrophosphatases; D012326:RNA Splicing; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D000255:Adenosine Triphosphate; D010744:Phosphoric Monoester Hydrolases; D000251:Adenosine Triphosphatases; C117634:ENTPD5 protein, human; D011755:Pyrophosphatases; C027201:ectoATPase