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NAGPA  -  N-acetylglucosamine-1-phosphodiester alpha...

Homo sapiens

Synonyms: APAA, Mannose 6-phosphate-uncovering enzyme, Phosphodiester alpha-GlcNAcase, UCE
 
 
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Disease relevance of NAGPA

  • To assess whether the PG-M3 MoAb could assist in the diagnosis of APL (M3), bone marrow and/or peripheral blood samples from 100 cases of acute nonlymphoid leukemias of different subtypes were blindly immunostained with the PG-M3 MoAb, using the immunoalkaline phosphatase (APAAP) or immunofluorescence technique as detection system [1].
  • To evaluate the clinical significance of the expression of epidermal growth factor receptor (EGFr) in oral squamous cell carcinoma (SCC), 100 formalin-fixed, paraffin-embedded cases of this tumour and ten samples of normal oral mucosa were immunostained with a monoclonal anti-EGFr antibody using an immunoalkaline phosphatase (APAAP) technique [2].
  • Comparisons of last 14-day, least-squares means among groups did not reveal differences in data treated by lean body weight [3MH/(kg LBW X d)] or by urinary creatinine excretion [3MH/(kg UCE X d)], but 3MH/(kg LBW X d) excretions were higher for exercise than no-exercise subjects [3].
  • Individual breast cancer cells were identified by F(ab) fragments of the pan-cytokeratin (CK) monoclonal antibody (MAb) A45-B/B3, directly conjugated with alkaline phosphatase, which identified cancer cells as sensitively as the standard APAAP procedure (r = 0.998; p < 0.0001) [4].
  • Eight carcinomas were completely negative for class I by the APAAP technique [5].
 

High impact information on NAGPA

  • The human ribosomal RNA promoter contains two distinct control elements (UCE and core) both of which are recognized by the sequence-specific DNA binding protein UBF1, which has now been purified to apparent homogeneity [6].
  • APAAP labelling of blood and bone-marrow samples for phenotyping leukaemia [7].
  • All positive results were further confirmed in enriched B-cell populations by antigen determination using immunostaining with the APAAP technique [8].
  • For tumor-cell detection, we applied the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique with monoclonal antibody Ber-Ep4 against two glycoproteins of 34 and 49 kd present of the surface and cytoplasm of epithelial cells [9].
  • UCE also hydrolyzes UDP-GlcNAc, a sugar donor for Golgi N-acetylglucosaminyltransferases [10].
 

Chemical compound and disease context of NAGPA

 

Biological context of NAGPA

  • The cytosolic domain of UCE contains two potential endocytosis motifs: (488)YHPL and C-terminal (511)NPFKD [14].
  • A crucial step in lysosomal biogenesis is catalyzed by "uncovering" enzyme (UCE), which removes a covering N-acetylglucosamine from the mannose 6-phosphate (Man-6-P) recognition marker on lysosomal hydrolases [14].
  • Further, immunophenotype and genotype of the cells were simultaneously examined with alkaline phosphatase anti-alkaline phosphatase (APAAP) immunostaining and FISH [15].
  • Cell surface antigens could be demonstrated with most immunocytochemical methods: however, the APAAP method was preferred for its sensitivity and effectiveness when combined with enzyme cytochemistry [16].
  • Bcl2, bax, and fas oncogene expression were also evaluated by the APAAP method [17].
 

Anatomical context of NAGPA

  • YHPL is shown to be the more potent of the two in retrieval of UCE from the plasma membrane [14].
  • COS cells transfected with the human cDNA expressed 50-100-fold increases in phosphodiester alpha-GlcNAcase activity proving that the cDNA encodes the subunits of the tetrameric enzyme [18].
  • A green-fluorescent protein-UCE transmembrane-cytosolic domain fusion protein colocalizes with TGN 46, as does endogenous UCE in HeLa cells, showing that the transmembrane and cytosolic domains determine intracellular location [14].
  • The human mannose 6-phosphate uncovering enzyme participates in the uncovering of the mannose 6-phosphate recognition tag on lysosomal enzymes, a process that facilitates recognition of those enzymes by mannose 6-phosphate receptors to ensure delivery to lysosomes [19].
  • One sample was processed for morphological examination, the other for frozen section immunohistology, using a panel of monoclonal antibodies (MAB) reacting with lymphocyte and macrophage determinants, detected by the immuno-alkaline-phosphatase (APAAP) method [20].
 

Associations of NAGPA with chemical compounds

  • We have isolated and sequenced human cDNA and mouse genomic DNA clones encoding N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (phosphodiester alpha-GlcNAcase) which catalyzes the second step in the synthesis of the mannose 6-phosphate recognition signal on lysosomal enzymes [18].
  • Two enzymes act sequentially to catalyze the addition of mannose 6-phosphate groups to the proteins: N-acetylglucosamine phosphotransferase (GlcNAc phosphotransferase) and N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (phosphodiester alpha-GlcNAcase) [21].
  • The presence of the MDR-1 gene product, a 170-kd glycoprotein (P-170), was analyzed in bone marrow plasma cells by means of the alkaline phosphatase (APAAP) technique using the P-170-specific monoclonal antibody (MoAb) C219 [22].
  • Trends of exercise- or protein intake-enhanced 3MH excretion could be masked by data as 3MH/(g UCE X d) if exercise or 3 X RDA protein intake can expand the body creatine pool independent of skeletal muscle mass [3].
  • METHODS: Immunohistochemical analysis using alkaline phosphatase anti-alkaline phosphatase (APAAP) was performed on formalin fixed, paraffin embedded lung tissues from 13 patients with LIP using anti-LMP1 and anti-bcl-2 monoclonal antibodies [23].
 

Regulatory relationships of NAGPA

  • The experiments were performed by the alkaline-antialkaline phosphatase (APAAP) technique by staining air-dried acetone-fixed cytospins and by dual-color immunofluorescent assay by staining mononuclear cell suspensions with monoclonal antibodies detecting BCL2 protein and antigens expressed by different hematopoietic subsets [24].
  • IgE-bearing and Fc epsilon RII-expressing cells were demonstrated in the upper dermis and along the BMZ in seven of 11 biopsy specimens by the APAAP technique [25].
  • The expression of the transferrin receptor (TfR) was studied in the acute leukaemias and lymphoproliferative disorders by means of indirect immunofluorescence and/or the enhanced alkaline phosphatase anti-alkaline phosphatase (APAAP) techniques using monoclonal antibodies to the receptor [26].
 

Other interactions of NAGPA

  • The expression of both p55 TNF-R and p75 TNF-R was determined using alkaline phosphatase-conjugated mouse anti-alkaline phosphatase (APAAP) and double immunofluorescence staining techniques with monoclonal antibodies [27].
  • We found clear positivity of thyroid follicular cells for B7.1 in HT but not in GD, nor in nonautoimmune specimens (NTG, PC) using in situ analysis by alkaline phosphatase anti-alkaline phosphatase (APAAP) technique [28].
  • A series of 60 primary laryngeal and hypopharyngeal tumours, 24 lymph node metastases and normal tissue were evaluated in frozen sections for the expression of MHC class I antigens, using monoclonal antibodies and the APAAP technique [29].
  • EXPERIMENTAL DESIGN: For the evaluation of VCAM-1 expression in rheumatoid synovium, this molecule has been demonstrated by alkaline phosphatase anti-alkaline phosphatase (APAAP) technique [30].
  • The target cells for infection were shown to be macrophages by immunohistochemistry (APAAP), dual immunofluorescence staining (using CD68 and p24) and electron microscopy [31].
 

Analytical, diagnostic and therapeutic context of NAGPA

  • Molecular cloning and functional expression of two splice forms of human N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase [18].
  • The protein observed after renaturation and subsequent SDS-PAGE and silver staining had an apparent molecular mass of 118 kDa, which is slightly smaller than bovine liver phosphodiester alpha-GlcNAcase (Mullis et al. (1994) J. Biol. Chem. 269, 1718-1726) [21].
  • Since the technique can be used on blood and marrow smears even after storage or postal transport, it is suggested that APAAP labelling should become the method of choice for immunophenotyping neoplastic samples in many haematology laboratories not equipped with specialised immunological diagnostic facilities [7].
  • Immunophenotyping results using the APAAP technique were comparable with those obtained with flow cytometry [32].
  • HSP expression was determined by alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunohistochemistry, using appropriate monoclonal antibodies and scored semiquantitatively [33].

References

  1. Immunocytochemical diagnosis of acute promyelocytic leukemia (M3) with the monoclonal antibody PG-M3 (anti-PML). Falini, B., Flenghi, L., Fagioli, M., Lo Coco, F., Cordone, I., Diverio, D., Pasqualucci, L., Biondi, A., Riganelli, D., Orleth, A., Liso, A., Martelli, M.F., Pelicci, P.G., Pileri, S. Blood (1997) [Pubmed]
  2. Prognostic implications of epidermal growth factor receptor immunoreactivity in squamous cell carcinoma of the oral mucosa. Maiorano, E., Favia, G., Maisonneuve, P., Viale, G. J. Pathol. (1998) [Pubmed]
  3. Exercise and protein intake effects on urinary 3-methylhistidine excretion. Hickson, J.F., Hinkelmann, K. Am. J. Clin. Nutr. (1985) [Pubmed]
  4. Tumor-antigen heterogeneity of disseminated breast cancer cells: implications for immunotherapy of minimal residual disease. Braun, S., Hepp, F., Sommer, H.L., Pantel, K. Int. J. Cancer (1999) [Pubmed]
  5. K-ras mutations (codon 12) are not involved in down-regulation of MHC class-I genes in colon carcinomas. Oliva, M.R., Cabrera, T., Esquivias, J., Perez-Ayala, M., Redondo, M., Ruiz-Cabello, F., Garrido, F. Int. J. Cancer (1990) [Pubmed]
  6. Functional cooperativity between transcription factors UBF1 and SL1 mediates human ribosomal RNA synthesis. Bell, S.P., Learned, R.M., Jantzen, H.M., Tjian, R. Science (1988) [Pubmed]
  7. APAAP labelling of blood and bone-marrow samples for phenotyping leukaemia. Erber, W.N., Mynheer, L.C., Mason, D.Y. Lancet (1986) [Pubmed]
  8. Lytic replication of Epstein-Barr virus in the peripheral blood: analysis of viral gene expression in B lymphocytes during infectious mononucleosis and in the normal carrier state. Prang, N.S., Hornef, M.W., Jäger, M., Wagner, H.J., Wolf, H., Schwarzmann, F.M. Blood (1997) [Pubmed]
  9. Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small-cell lung cancer. Passlick, B., Izbicki, J.R., Kubuschok, B., Nathrath, W., Thetter, O., Pichlmeier, U., Schweiberer, L., Riethmüller, G., Pantel, K. J. Clin. Oncol. (1994) [Pubmed]
  10. Human mannose 6-phosphate-uncovering enzyme is synthesized as a proenzyme that is activated by the endoprotease furin. Do, H., Lee, W.S., Ghosh, P., Hollowell, T., Canfield, W., Kornfeld, S. J. Biol. Chem. (2002) [Pubmed]
  11. The expression of the multidrug transporter P-170 glycoprotein in remission phase is associated with early and resistant relapse in multiple myeloma. Musto, P., Lombardi, G., Matera, R., Carotenuto, M. Haematologica (1991) [Pubmed]
  12. Absence of MHC class II antigen on mast cells at sites of inflammation in human skin. Lipski, S., Grabbe, J., Henz, B.M. Exp. Dermatol. (1996) [Pubmed]
  13. Evolution of bone marrow fibrosis and stromal antigenic expression in chronic myeloid leukemia on alpha interferon and Ara-C therapy. Straetmans, N., Ma, D.D., Nevell, D.F., Arthur, C. Hematopathology and molecular hematology. (1996) [Pubmed]
  14. Lysosomal hydrolase mannose 6-phosphate uncovering enzyme resides in the trans-Golgi network. Rohrer, J., Kornfeld, R. Mol. Biol. Cell (2001) [Pubmed]
  15. Cytogenetic clonality analysis in myelodysplastic syndrome: monosomy 7 can be demonstrated in the myeloid and in the lymphoid lineage. van Lom, K., Hagemeijer, A., Smit, E., Hählen, K., Groeneveld, K., Löwenberg, B. Leukemia (1995) [Pubmed]
  16. A combined cytochemical and immunocytochemical method for simultaneous visualization of cytoplasmic enzyme reactivity and cell surface antigens in cell suspensions. Gloghini, A., Cozzi, M., Sulfaro, S., Volpe, R., Carbone, A. Am. J. Clin. Pathol. (1989) [Pubmed]
  17. Induction of apoptosis by monosaccharide butyrate stable derivatives in chronic lymphocytic leukemia cells. Santini, V., Gozzini, A., Scappini, B., Caporale, R., Zoccolante, A., Rigacci, L., Gelardi, E., Grossi, A., Alterini, R., Ferrini, P.R. Haematologica (1999) [Pubmed]
  18. Molecular cloning and functional expression of two splice forms of human N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase. Kornfeld, R., Bao, M., Brewer, K., Noll, C., Canfield, W. J. Biol. Chem. (1999) [Pubmed]
  19. Characterization of the TGN exit signal of the human mannose 6-phosphate uncovering enzyme. Nair, P., Schaub, B.E., Huang, K., Chen, X., Murphy, R.F., Griffith, J.M., Geuze, H.J., Rohrer, J. J. Cell. Sci. (2005) [Pubmed]
  20. An immunocytochemical study of lymphocyte and macrophage populations in the bone marrow of patients with non-Hodgkin's lymphoma. Nash, J.R., Smith, S.R., Mackie, M.J. J. Pathol. (1988) [Pubmed]
  21. Purification and characterization of human serum N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase. Lee, J.K., Pierce, M. Arch. Biochem. Biophys. (1995) [Pubmed]
  22. MDR-1 expression and response to vincristine, doxorubicin, and dexamethasone chemotherapy in multiple myeloma refractory to alkylating agents. Cornelissen, J.J., Sonneveld, P., Schoester, M., Raaijmakers, H.G., Nieuwenhuis, H.K., Dekker, A.W., Lokhorst, H.M. J. Clin. Oncol. (1994) [Pubmed]
  23. Expression of bcl-2 and Epstein-Barr virus LMP1 in lymphocytic interstitial pneumonia. Kaan, P.M., Hegele, R.G., Hayashi, S., Hogg, J.C. Thorax (1997) [Pubmed]
  24. BCL2 oncogene protein expression in human hematopoietic precursors during fetal life. Bonati, A., Albertini, R., Garau, D., Pinelli, S., Lunghi, P., Almici, C., Carlo-Stella, C., Rizzoli, V., Dall'Aglio, P. Exp. Hematol. (1996) [Pubmed]
  25. IgE and its related phenomena in bullous pemphigoid. Soh, H., Hosokawa, H., Asada, Y. Br. J. Dermatol. (1993) [Pubmed]
  26. Transferrin receptor expression in the leukaemias and lymphoproliferative disorders. Barnett, D., Wilson, G.A., Lawrence, A.C., Buckley, G.A. Clinical and laboratory haematology. (1987) [Pubmed]
  27. Localization of tumor necrosis factor receptors in the synovial tissue and cartilage-pannus junction in patients with rheumatoid arthritis. Implications for local actions of tumor necrosis factor alpha. Deleuran, B.W., Chu, C.Q., Field, M., Brennan, F.M., Mitchell, T., Feldmann, M., Maini, R.N. Arthritis Rheum. (1992) [Pubmed]
  28. B7.1 costimulatory molecule is expressed on thyroid follicular cells in Hashimoto's thyroiditis, but not in Graves' disease. Battifora, M., Pesce, G., Paolieri, F., Fiorino, N., Giordano, C., Riccio, A.M., Torre, G., Olive, D., Bagnasco, M. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  29. Lack of MHC class I antigens and tumour aggressiveness of the squamous cell carcinoma of the larynx. Esteban, F., Concha, A., Delgado, M., Pérez-Ayala, M., Ruiz-Cabello, F., Garrido, F. Br. J. Cancer (1990) [Pubmed]
  30. Expression of vascular cell adhesion molecule-1 mRNA and protein in rheumatoid synovium demonstrated by in situ hybridization and immunohistochemistry. Kriegsmann, J., Keyszer, G.M., Geiler, T., Bräuer, R., Gay, R.E., Gay, S. Lab. Invest. (1995) [Pubmed]
  31. Macrophages are the major target cell for HIV infection in long-term marrow culture and demonstrate dual susceptibility to lymphocytotropic and monocytotropic strains of HIV-1. Gill, V., Shattock, R.J., Freeman, A.R., Robinson, G., Griffin, G.E., Gordon-Smith, E.C., Gibson, F.M. Br. J. Haematol. (1996) [Pubmed]
  32. Immunophenotyping of acute myeloid leukemia using monoclonal antibodies and the alkaline phosphatase-antialkaline phosphatase technique. Hanson, C.A., Gajl-Peczalska, K.J., Parkin, J.L., Brunning, R.D. Blood (1987) [Pubmed]
  33. Heat shock protein expression in the eye and in uveal melanoma. Missotten, G.S., Journée-de Korver, J.G., de Wolff-Rouendaal, D., Keunen, J.E., Schlingemann, R.O., Jager, M.J. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
 
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