Disease relevance of ENTPD5

• In addition, detection of altered PCPH polypeptides by Western analysis potentially can be applied to the early identification of laryngeal squamous cell carcinoma [1].
• Furthermore, PCPH expression decreased parallel to the increase in cellular atypia of the dysplastic samples: PCPH either was expressed at very low levels or not expressed in cases of severe dysplasia/carcinoma in situ [1].
• This trend toward loss of PCPH expression along malignant progression of the larynx was confirmed by the low to null expression of PCPH in samples of invasive laryngeal carcinoma and by the complete absence of PCPH immunostaining in a laryngeal carcinoma-derived liver metastasis [1].
• Collectively, these results positively identify PCPH as a good early molecular marker for testicular neoplasms, and strongly indicate that immunodetection of truncated PCPH polypeptides may be a useful diagnostic tool for TGCT [2].
• Our previous studies on the involvement of PCPH in human cancer showed that human breast tumor cell lines have frequent alterations in PCPH, including multiple PCPH polypeptide forms that are not expressed in normal cells [3].

High impact information on ENTPD5

• The close topological association of both galactosyltransferase and thiamine pyrophosphatase (or nucleoside diphosphatase) suggests a concerted action of both enzymes in glycosylation [4].
• The PCPH oncoprotein antagonizes the proapoptotic role of the mammalian target of rapamycin in the response of normal fibroblasts to ionizing radiation [5].
• Furthermore, the proapoptotic function of mTOR was also antagonized by the expression in MEF3T3 cells of the PCPH oncoprotein, known to enhance cell survival by causing partial ATP depletion [5].
• Previous reports from our laboratory described the activation of the PCPH gene into the PCPH oncogene (mt-PCPH, reported previously as Cph) by a single point mutational deletion [6].
• However, despite this overall negative regulatory role on Ras signaling, mt-PCPH, but not PCPH, cooperated with the Ras oncoprotein to produce a prolonged stimulation of the phosphorylation of ERK1 but had no effect on the phosphorylation levels of ERK2 [6].

Biological context of ENTPD5

• CD39-L4 is a secreted human apyrase, specific for the hydrolysis of nucleoside diphosphates [7].
• CD39L2, CD39L3, and CD39L4 were mapped on the human genome, and the murine homologues identified with the putative map locations were assigned on the basis of regions of conserved gene order between human and mouse chromosomes [8].
• Activity measurements of CD39L4 isolated from tunicamycin-treated, transiently transfected COS-7 cells indicate that glycosylation is not required for full ADPase activity [9].
• Our results should prove instrumental in designing studies to define the cellular function of the human PCPH proto-oncogene [10].
• These data provide suggestive evidence for a possible association of the lack of PCPH expression to the neoplastic phenotype of human tumor cells [10].

Anatomical context of ENTPD5

• COS-7 cells transfected with a CD39-L4 expression construct utilizing the naturally occurring leader peptide express recombinant protein outside of the cells [7].
• We also demonstrate expression of CD39-L4 message in macrophages, suggesting that the protein is present in the circulation [7].
• In this study, stable mammalian and insect cell lines were generated expressing CD39L4 protein to purify and characterize the recombinant protein [9].
• Immunohistochemical data showed that, compared with normal laryngeal mucosa, PCPH expression in the dysplastic samples was associated with areas of epithelial cell maturation rather than with regions of increased proliferation [1].
• PCPH is a gene involved in the regulation of eukaryotic cell proliferation and stress response [1].

Associations of ENTPD5 with chemical compounds

• We determined that the monomer is the most active form of CD39L4 by measuring the activity of sucrose density gradient fractions of monomers and partially purified dimers [9].
• CD39L4 is a soluble E-nucleoside triphosphate dephosphohydrolase (E-NTPDase) with specificity for nucleotide diphosphates (NDPs) [9].
• We put forward the notion that expression of oncogenic forms of the PCPH gene, which are known to confer resistance to radiation and chemotherapeutic drugs, including cisplatin, may be expressed in TGCTs, and thus contribute to the development of therapeutic resistance [2].
• In addition, comparing the biochemical properties of wild-type NTPDase5 and those of a mutant NTPDase5 (C15S, which lacks the single, non-conserved cysteine residue), also expressed in bacteria, suggests that Cys15 is not essential for either proper refolding or enzymatic activity (indicating this residue is not involved in a disulfide bond) [11].
• Uridine diphosphate glucose-sterol glucosyltransferase and nucleoside diphosphatase activities in etiolated pea seedlings [12].

Other interactions of ENTPD5

• CD39-L2 and CD39-L4 genes encode hydrophobic portions in their amino termini, suggesting that they might encode secreted apyrases [7].
• When denatured by SDS under nonreducing conditions, a fraction of the CD39L4 protein migrates as a 110 kDa disulfide-linked dimer [9].
• Of several nucleoside diphosphatase activities, UDPase activity is most enhanced by the freeze-thaw and sucrose-density-gradient-fractionation procedures [12].
• Nucleoside diphosphatase (NDPase) activity, using inosine diphosphate (IDP) and thiamine pyrophosphate (TPP) as substrates, was observed in the Golgi apparatus, with a gradient of increasing reaction product noted in some cells from the cis to trans cisternae [13].
• Sialyltransferase and nucleoside diphosphatase as markers for tumor monitoring [14].

Analytical, diagnostic and therapeutic context of ENTPD5

• The human homolog was localized by radiation-hybrid mapping to chromosome band 14q24.3, a region syntenic to the Pcph location on mouse chromosome 12 [10].
• To begin testing this concept, we studied PCPH expression in human TGCT cell lines and in 54 solid tumors by RT-PCR, western immunoblot and immunohistochemistry [2].
• Western blot analyses of the same set of samples detected a 47 kDa form as the main PCPH polypeptide present in all cases studied [15].
• We performed a study on the expression of the PCPH protein in samples corresponding to normal, pre-malignant and malignant stages of the human mammary gland by using protocols of immunohistochemistry and Western blot analysis with anti-PCPH specific antibodies [15].
• Applying nucleoside diphosphatase (NDPase) histochemistry, the appearance and differentiation of microglial cells in the developing human cerebral hemispheres were investigated by light and electron microscopy [16].

References