Disease relevance of NME2P1

• NM23-H2, a presumed regulator of tumor metastasis in humans, is a hexameric protein with both enzymatic (NDP kinase) and regulatory (transcriptional activation) activity [1].
• Our results confirm that NDP-kinase expression increases in malignant cells of breast carcinomas, but cannot be considered as a biological marker of metastatic dissemination [2].
• Here, we have characterized the kinase activity and DNA processing functions of eight human proteins that contain at least one domain homologous to Escherichia coli NDK [3].
• Immunohistochemical analysis with anti-rat NDP kinase (NDP kinase alpha, NDP kinase beta) monoclonal antibodies was performed in deparaffinized sections of 56 specimens of oral squamous cell carcinoma [4].
• Immunohistochemical analysis of nm23/NDP kinase expression in human lung adenocarcinoma: association with tumor progression in Clara cell type [5].

High impact information on NME2P1

• The relative staining intensities were evaluated by comparing primary tumor sites with adjacent nontumorous liver tissue or with metastatic sites, RESULTS: The expression of NDP kinase in primary sites in patients with distant metastases was significantly less intense than that in patients without distant metastases (P = .018) [6].
• CONCLUSION: These results suggest that the reduced expression of NDP kinase is closely associated with distant metastatic potential in hepatocellular carcinoma [6].
• The intensity of NDP kinase expression did not statistically correlate with tumor size or number of lesions in the liver, histopathological classification of tumor, associated liver diseases, hepatitis virus markers, or tumor markers [6].
• Involvement of NM23/NDP kinase in a DNA repair pathway would be consistent with its role in normal and tumor cell development [7].
• Catalysis of DNA cleavage and nucleoside triphosphate synthesis by NM23-H2/NDP kinase share an active site that implies a DNA repair function [7].

Chemical compound and disease context of NME2P1

• Meanwhile, all of the recombinant mutant Nm23-H1 proteins produced in Escherichia coli exhibited NDP kinase activity levels at the wild type protein, although the P96S and S120G mutant proteins exhibited decreased histidine protein kinase activity and autophosphorylation level, respectively [8].
• Under the same experimental conditions, the anti-herpetic (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) derivative was efficiently converted to BVDU-MP and BVDU-DP by both VZV TK and HSV-1 TK and further, into BVDU-TP, by NDP kinase [9].
• To contribute to the studies for the development of a universal vaccine, the occurrence of antibodies (Ab) against three HIV-1 strains (MN, BRU and NDK) was determined in serum samples from 85 HIV-1-positive patients, adult volunteers seen at the University Hospital of the Faculty of Medicine of Ribeirão Preto-USP [10].

Biological context of NME2P1

• Nm23/NDP kinase isoforms may have specific functions in the phosphotransfer network involved in spermiogenesis and flagellar movement [11].
• No correlation was found between NDP-kinase activity and S phase, taken as an index of cell proliferation [2].
• These data support a model in which NM23/NDP kinase modulates gene expression through DNA binding and subsequent structural transactions [12].
• This methodology was also applied to in vivo phosphorylation studies of C. albicans NDP kinase [13].
• In this enzyme, autophosphorylation of active site histidine is an accepted intermediate step in the catalytic phosphate transfer activity of nucleoside diphosphate kinase (NDP kinase) [13].

Anatomical context of NME2P1

• Based upon the surface expression of nm23/NDP kinase, cells were classified as nm23-H1+H2-, nm23-H1+H2+ or nm23-H1-H2-. No cell lines with nm23-H1-H2+ were found among those examined [14].
• Both membrane and cytosolic fractions of human neutrophils were found to contain NDP kinase activity [15].
• Interestingly, stimulation with N-formylmethionyl leucylphenylalanine in the presence of cytochalasin B showed an increase in membrane NDP kinase activity together with the translocation of the enzyme from the cytosol to the membrane, suggesting a possible role of NDP kinase in regulating G-proteins as previously reported [15].
• In addition, there was also no significant difference in the nm23-H1/NDP kinase staining intensity of primary and metastatic lymph node lesions of tumors with lymph node metastases [16].
• We found that normal thyroid epithelial cells were stained weakly but homogeneously by mouse monoclonal anti-nm23-H1/NDP kinase antibody [16].

Associations of NME2P1 with chemical compounds

• Our results reveal that there are no significant changes between the two enzyme versions even in the surroundings of the catalytic histidine that is required for NDP kinase activity [17].
• Several biochemical activities have been reported for Nm23, including NDP kinase activity, serine autophosphorylation and protein-histidine kinase activity [18].
• Moreover, no correlation was observed between NDP-kinase activity and tumor size, histoprognostic index, estrogen receptors or progesterone receptors [2].
• NDP kinase CDelta had similar kinetic properties to the major human NDP kinases A and B, but was significantly more stable to denaturation by urea and heat [19].
• Overnight incubation of formalin-fixed tumor sections at 4 degree C with primary rabbit polyclonal IgG antibody to human nm23-H1/NDP kinase was followed by detection with standard ABC method [20].

Regulatory relationships of NME2P1

• Native human erythrocyte NDP kinase protein inhibited the induction of erythroid differentiation of HEL, KU812 and K562 cells, but not the induction of monocytic or granulocytic differentiation of HL-60, U937 and HEL/S cells [21].
• By modifying cytoskeleton organization and protein trafficking, some NDP kinase isoforms may indirectly promote adhesion to the extracellular matrix in some cell types [22].

Other interactions of NME2P1

• NM23-H2 is a human NDP kinase [23].
• Therefore, p16 may be a unique Nm23/NDP kinase that functions as an accessory protein for cytosolic Hsc70 in eukaryotes [24].
• NM23 is a candidate tumor suppressor protein and has recently been identified as an NDP kinase [25].
• The structural information of NDP kinase obtained by analysis using capillary electrophoresis is valuable for understanding its suggested biological function as a tumor metastasis suppressor and c-myc transcription factor, etc [26].
• Moreover, both the mutant nm23-H2His protein and truncated nm23-H2 protein containing N-terminal (1-60) peptide, which do not have NDP kinase activity, also inhibited erythroid differentiation of HEL cells [21].

Analytical, diagnostic and therapeutic context of NME2P1

• Site-directed mutagenesis, competition assays between wild-type and mutant NDK proteins, and NMR studies confirmed that the DNA-binding and 3' --> 5' exonuclease activity of human NDK1 is an intrinsic activity of the protein [3].
• Capillary electrophoresis was used to monitor the quaternary structure and structural changes by denaturants of nucleoside diphosphate kinase (NDP kinase) [26].
• The enhanced NDP kinase accumulation was demonstrated in the matured osteoblasts in vivo and in vitro by immunohistochemistry [27].
• From a series of tumor cohort studies, low expression of Nm23/NDP kinase has been correlated with poor patient prognosis and survival, lymph node infiltration, and histopathological indicators of high metastatic potential in a number of cancer types, including mammary and ovarian carcinomas and melanoma [28].
• Comparison of the molecular weights of the NDP kinase monomer determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) (23,000) and of the oligomer determined by sedimentation equilibrium experiments (125,000) indicated that the oligomer is a hexamer [29].

References