Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.23.5 (cathepsin D)
4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cathepsin D from porcine spleen contained mannose (3.3%), glucosamine (1.4%), and mannose 6-phosphate (0.08%). Essentially all of the oligosaccharides of cathepsin D could be released by endo-beta-N-acetylglucosaminidase H, pointing to oligomannoside types of structures. Three neutral oligosaccharide fractions, containing 5, 6, and 7 mannose residues, respectively, were isolated by gel permeation chromatography on Bio-Gel P-2. Studies using exoglycosidase digestions and 500-MHz 1H NMR spectroscopy revealed that their structures are [Man alpha 1 leads to 2]0 or 1 Man alpha 1 leads to 6[Man alpha 1 leads to 3]Man alpha 1 leads to 6[Man alpha 1 leads to 2)0 or 1 Man alpha 1 leads to 3]Man beta 1 leads to 4GlcNAc beta 1 leads to 4 GlcNAc. These structures are identical to what have recently been proposed by Takahashi et al. for the major oligosaccharide units of cathepsin D from the same source (T. Takahashi, P. G. Schimidt, and J. Tang (1983) J. Biol. Chem. 258, 2819-2930), except for the occurrence of two isomeric oligosaccharides containing six mannoses. Only a part (3.4%) of the oligosaccharides were acidic, containing phosphates in monoester linkage. The phosphorylated oligosaccharides also consisted of oligomannoside-type chains which were analogous to, but more heterogeneous in size than the neutral oligosaccharides. Cathepsin D was bound to a mannose- and N-acetylglucosamine-specific lectin (mannan-binding protein) isolated from rabbit liver with the Ki value of 5.4 X 10(-6) M.
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PMID:Oligosaccharides on cathepsin D from porcine spleen. 642 53

Chicken vitellogenin, a serum lipoprotein specific for laying hens, has been thought to be proteolytically cleaved into the heavy and light chain lipovitellins and phosvitin, the major yolk granule proteins, during or after transportation into oocyte. In this study, another proteolytic product of vitellogenin has newly been isolated from the 'beta-livetin' fraction of yolk plasma. It is a yolk glycoprotein of 40 kDa (YGP40) with asparagine-linked carbohydrate chain(s) recognized by Concanavalin A and castor bean lectin (RCA-I), and it is identified as a C-terminal cysteine-rich fragment of the major vitellogenin (vitellogenin II), the cysteine-rich domain homologous to D2 region of von Willebrand factor. Another yolk plasma glycoprotein of 42 kDa is suggested to be one of the proteolytic products of the minor vitellogenin (vitellogenin I). Both 40 kDa and 42 kDa glycoproteins were shown to be present in growing oocytes but absent in laying hen's serum. Limited proteolysis of vitellogenin II with cathepsin D produced a 40 kDa protein with reactivity to anti-YGP40 antibody. Gel filtration analysis of vitellogenin II digested with cathepsin D showed that YGP40 dissociated from lipovitellin-phosvitin complex after the proteolytic cleavage. These results suggest that after incorporation from serum via a specific receptor vitellogenin II is cleaved in the oocyte into four fragments, heavy and light chain lipovitellins, phosvitin and YGP40, and that YGP40 is released into the yolk plasma before or during compartmentation of lipovitellin-phosvitin complex into the yolk granule.
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PMID:Precursor-product relationship between chicken vitellogenin and the yolk proteins: the 40 kDa yolk plasma glycoprotein is derived from the C-terminal cysteine-rich domain of vitellogenin II. 759 59

Leishmania major promastigotes, when grown in the presence of tunicamycin (TM), produced a plasma membrane-bound, proteolytically active gp63 with a lower molecular weight than the native glycoprotein. However, this lower molecular weight form of gp63 continued to be recognized by concanavalin A (Con A), suggesting that inhibition of N-linked glycosylation was not complete. Metabolic labeling of gp63, using [35S]methionine, demonstrated that in the range of 5-10 micrograms ml-1 TM, only the lower molecular weight form was synthesized, suggesting that inhibition was complete and that lectin binding was likely due to the GPI anchored sugars. Removal of the oligosaccharides from L. major and L. mexicana amazonensis promastigotes using endoglycosidase F, caused the gp63 molecular weight to decrease to the same value observed in the presence of TM, once again without affecting the proteolytic activity. However, this deglycosylated enzyme continued to bind Con A until subsequently treated with periodate. The latter oxidation reaction resulted in complete loss of Con A binding without inhibiting the protease activity or the substrate specificity of gp63. Further investigations revealed that both glycosylated and deglycosylated gp63 were resistant to proteolytic digestion by either autolysis or cathepsin D. These findings indicate that the N-linked oligosaccharides of gp63 are not essential for folding, transport, maintenance of enzyme activity or resistance to proteolysis.
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PMID:An investigation into the significance of the N-linked oligosaccharides of Leishmania gp63. 818 21

Expression of beta 1-6 branched oligosaccharides in human breast cancer cells was investigated in vivo and in vitro. Lectin histochemical and lectin blotting analyses of surgically resected specimens were performed using L-PHA (phaseolus vulgaris leukoagglutinin) lectin, which binds to beta 1-6 oligosaccharides. The glycoproteins bearing beta 1-6 oligosaccharides of breast cancer tissues were found to be 170 kD and 120 kD in molecular weight, and the former appeared to be an epitope of carcinoembryonic antigen (CEA). The beta 1-6 oligosaccharides were expressed in both cancer cell lines at the outer layer of the colonies when cultured in type I collagen, but not in agarose gel. No correlation was observed between beta 1-6 expression and cell cycle. The beta 1-6 oligosaccharides did not coincide with breast cancer-associated antigens, such as CEA, MUC1, and cathepsin D. The beta 1-6 oligosaccharides of these cell lines were markedly inhibited when swainsonine, a mannosidase II inhibitor, was added to the culture medium. The 120 kD molecule, which was obtained from MCF-7 cells cultured in type I collagen gel, was consistent with that of breast cancer tissues and was similar to lysosome-associated membrane glycoproteins (LAMPs). The results suggest that the glycoproteins bearing beta 1-6 branched oligosaccharides in human breast cancer incorporate an epitope of CEA and human LAMPs and that the expression of LAMPs may depend on their surrounding matrices and may play an important role in cancer invasion or metastasis.
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PMID:Expression of L-PHA-binding proteins in breast cancer: reconstitution and molecular characterization of beta 1-6 branched oligosaccharides in three-dimensional cell culture. 873 85

The lysosomal aspartyl protease cathepsin D is present in most mammalian cells and is active in the catabolism of intracellular and endocytosed proteins. It appears to be overexpressed and abnormally secreted in breast cancer cells, and may contribute to the process of tumor metastasis. In the present study, cathepsin D was purified 4500-fold from normal human breast tissue using pepstatin-agarose, DEAE Sephadex, and Sephadex G-75 chromatography. The resulting enzyme on SDS-PAGE contained five protein bands (47, 31, 29, 13, and 12kDa) which were all immunoreactive on western blot analysis using anti-cathepsin D polyclonal antibodies. The isoform profile of purified cathepsin D consisted of three major peaks at approximate pI 7.3, 6.8, and 6.3, and a broad area of lower activity between pI of 5.0 and 2.0. The purified enzyme had a broad pH optimum centered around pH 3.3. Lectin blotting indicated that cathepsin D is a glycoprotein which is recognized by Galanthus nivalis agglutinin and concanavalin A, suggesting the presence of mannose residues. However, Sambucus nigra agglutinin, Tetragonolobus purpureas agglutinin, Triticum vulgaris agglutinin, and Erythrina cristagalli agglutinin failed to recognize cathepsin D, suggesting a lack of lectin-available sialic acid, fucose, N-acetylglucosamine, and galactose residues, respectively.
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PMID:Purification and characterization of cathepsin D from normal human breast tissue. 915 88

The aspartyl protease cathepsin D (EC 3.4.23.5) appears to be found in increased amounts and/or abnormally secreted in breast cancer cells, and may contribute to the metastatic spread of malignancy. In the present study, cathepsin D was purified 4800-fold in 20% yield from malignant human breast tissue using affinity chromatography on pepstatin-agarose and DEAE-Sephadex chromatography. Slab gel SDS-PAGE of the purified cathepsin D indicated the presence of three major protein bands (31, 13, 12, kDa) and two minor protein bands (47, 29 kDa). Western blotting indicated that the 31 kDa band was the major immunoreactive species. Isoelectric focusing indicated that the purified cathepsin D consisted of three major isoforms at approximate pIs of 7.4, 7.0 and 6.6, and a possible isoform of lower activity centered around pI 3.2. The pH curve of purified cathepsin D indicated a broad optimum centered around pH 3.4. Lectin blotting suggested the presence of mannose residues but no evidence was found for lectin-available sialic acid, fucose, N-acetylglucosamine and galactose residues. The investigated properties of purified cathepsin D from malignant breast tissue are very similar, if not identical, to the properties of cathepsin D previously purified from normal human breast tissue. Our findings suggest that the elevated activity and antigenic levels of cathepsin D in malignant breast tissue are due to increased amounts of apparently normal enzyme.
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PMID:Characterization of purified cathepsin D from malignant human breast tissue. 991 8

In tumor tissue specimens of 27 primary and 17 secondary glioblastomas and the precursor lesions, the immunohistochemical expression patterns of the membrane protein CD44s, the basal lamina proteins laminin, collagen IV, and fibronectin, the lectin galectin-3 recognizing tenascin and N-CAM as well as of the matrix-degrading enzymes matrix metalloproteinase MMP-2 and MMP-9, and cathepsin D were studied. Besides expression of basal lamina proteins in vessels, all glioblastomas and the precursor lesions showed strong immunoreactivity of CD44s, tenascin, galectin-3, and N-CAM which were restricted to solid tumor masses. Present in solid tumor areas, MMP-2, MMP-9 and cathepsin D were also strongly expressed by single tumors cells invading adjacent brain tissue at the infiltrative margin. Neither the expression pattern in primary and secondary glioblastomas nor in the precursor tumors revealed significant differences. There was also no intraindividual constant expression pattern during glioma progression or correlation with malignancy. Restricted expression of CD44s, galectin-3, tenascin and N-CAM in solid tumor masses seems to contribute to homotypic tumor cell adhesion while single tumor cells abolish this expression profile and acquire invasive activities by expression of cathepsin D, MMP-2 and MMP-9.
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PMID:Expression of adhesion factors and degrading proteins in primary and secondary glioblastomas and their precursor tumors. 1072 72

This study aims at the in situ identification of factors mediating glioma cell invasion requiring adhesion, extracellular matrix degradation, and migration. Forty-five gliomas (astrocytomas, glioblastomas, oligodendrogliomas, and mixed gliomas) were investigated for the immunohistochemical expression of the membrane protein CD44s, the basal lamina proteins laminin, collagen IV, and fibronectin, the lectin galectin-3 recognizing tenascin and N-CAM, as well as for the matrix-degrading enzymes metalloproteinases MMP-2, MMP-9, and cathepsin D. Besides vessels expressing basal lamina proteins, tenascin, MMP-2, MMP-9, and galectin-3, tumor cells revealed strong immunoreactivity for CD44s, tenascin, galectin-3, and N-CAM, which was restricted to solid tumor masses. Single invading cells displayed distinct expression of MMP-2 and MMP-9, also found in solid tumor areas, as well as of cathepsin D. Restricted expression of CD44s, galectin-3, tenascin, and N-CAM in solid tumor masses seems to contribute to homotypical tumor cell adhesion. However, switching to an invasive phenotype, single tumor cells lack this expression pattern and acquire degrading and phagocytic activities by expressing cathepsin D, MMP-2, and MMP-9, which are also expressed by solid tumor masses facilitating the loosening and invasion of single neoplastic cells. The blocking of these factors may be of potential benefit in anti-invasive therapy.
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PMID:Adhesive and invasive features in gliomas. 1108 57

To clarify the sorting mechanism of the lysosomal/granular proteoglycan serglycin, we treated human promonocytic U937 cells with p-nitrophenyl-beta-D-xyloside (PNP-xyl) and cycloheximide. In the absence of protein synthesis, the carbohydrate moiety of serglycin was synthesized as PNP-xyl-chondroitin sulfate (CS), and most of it was delivered to lysosomes and degraded. Further, an augmented lysosomal targeting of serglycin in the presence of tunicamycin suggested that a sorting/lectin receptor with multiple specificity was involved with an increased capacity for serglycin in the absence of N-glycosylation. Correspondingly, the cation-independent mannose 6-phosphate receptor (CI-MPR) and sortilin were observed to bind to immobilized CS. These receptors were eluted in the presence of 200-400 mM and 100-250 mM NaCl, respectively. After treating the cells with a cross-linking reagent, a portion of the sulfated proteoglycan was coimmunoprecipitated with the CI-MPR but not with sortilin. In the presence of phorbol ester, lysosomal targeting of serglycin and to a lesser extent, of cathepsin D was inhibited. We conclude that the CI-MPR participates in lysosomal and granular targeting of serglycin and basic proteins such as lysozyme associated with the proteoglycan in hematopoietic cells.
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PMID:The cation-independent mannose 6-phosphate receptor is involved in lysosomal delivery of serglycin. 1721 Jun 18

The poor prognosis of melanoma and the high cost of lymph node biopsy for melanoma patients have led to an urgent need for the discovery of convenient and accurate prognostic indicators. Here, we have developed a natural glycoprotein microarray to discover serum autoantibodies to distinguish between patients with node negative melanoma and node positive melanoma. Dual-lectin affinity chromatography was used to extract glycoproteins from a melanoma cell line. Liquid-based reverse phase separation and microarray platforms were then applied to separate and spot these natural proteins on nitrocellulose slides. The serum autoantibodies were investigated by exposing these proteins to sera from 43 patients that have already been diagnosed to have different stages of early melanoma. The combination of 9 fractions provides a 55% sensitivity with 100% specificity for the detection of node positive against node negative and a 62% sensitivity with 100% specificity for the detection of node negative against node positive. Recombinant proteins were used to confirm the results using a sample set with 79 patients with diagnosed melanoma. The response of sera against recombinant 94 kD glucose-regulated protein (GRP94), acid ceramidase (ASAH1), cathepsin D (CTSD), and lactate dehydrogenase B (LDHB) shared a similar pattern to the fractions where they were identified. The glycoarray platform provides a convenient and highly reproducible method to profile autoantibodies that could be used as serum biomarkers for prognosis of melanoma.
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PMID:Serum autoantibody profiling using a natural glycoprotein microarray for the prognosis of early melanoma. 2087 97


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