Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transmembrane domain of Golgi resident proteins such as beta-galactoside alpha 2,6-sialyltransferase (ST) and N-acetylglucosaminyltransferase 1 (NT) contain a Golgi retention signal which confers Golgi retention to reporter proteins appended to them in the appropriate context. Thus, chimeras of the cell surface protein dipeptidyl peptidase IV containing the transmembrane domain of ST and NT are retained in the Golgi apparatus in MDCK and COS cells, as assessed by indirect immunofluorescence microscopy. Transfection of these chimeric constructs into CHO cells, however, results in their transport to vesicular structures which do not colocalize with that of an endogenous Golgi marker, mannosidase II. Furthermore, the staining pattern of these structures are not affected by brefeldin A. Biochemical analysis of the transgene products in pulse-chase experiments revealed that the chimeric proteins eventually become resistant to endoglycosidase H, suggesting that they are transported beyond the medial Golgi and therefore the vesicular structures are likely to be post-Golgi. The vesicular structures colocalized well with a lysosomal marker, cathepsin D, and also with internalized FITC-dextran chased into the lysosomal compartment. Monitoring the cell surface appearance of the chimeric protein suggests that the majority is transported directly to the lysosomal compartment. Golgi retention can be completely restored for ST and improved for NT by the inclusion of sequences flanking the transmembrane domain. Our results reflect cell type differences in the interpretation of the transmembrane domain Golgi retention signal, established that general Golgi retention of type II glycosyltransferases requires the hydrophilic flanking sequence as well as the transmembrane domain, and demonstrate that proteins which escape Golgi retention may be channeled to the lysosomal pathway.
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PMID:Cell type differences in Golgi retention signals for transmembrane proteins. 765 2

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