Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00572 (Asn)
 11,732 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A glycoprotein has been isolated from the colonic lavages of healthy individuals that is immunologically equivalent to carcinoembryonic antigen purified from tumor tissue. The NH2-terminal sequence of the glycoprotein from normal colon lavages is Lys-Leu-Thr-lle-Glu-Ser-Thr-Pro-Phe-(Asn)-Val-Ala-Glu-Gly-Lys-Glu-Val-(Leu,lle)-(Leu,lle)-(Leu,lle)-Val-(His,Arg?)-?-(Leu,lle). This is homologous to the NH2-terminal sequence of 23 of the first 24 amino acids of carcinoembryonic antigen isolated from tumor tissue.
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PMID:Amino-terminal sequence of a carcinoembryonic antigen-like glycoprotein isolated from the colonic lavages of healthy individuals. 7 56

Studies of the chromatographic behavior of mammalian tRNAs, from several sources, on acylated DBAE-cellulose indicate that species of tRNA Asn , tRNA Asp and tRNA His can be retained on this matrix, while species of tRNA Tyr, tRNA Asn and tRNA Asp are not retained. Treatment of total rat liver tRNA with cyanogen bromide and subsequent chromatography on Aminex A-28 columns demonstrated that these tRNA species might contain Q (or Q*) nucleoside. However, comparable studies of the tRNA isolated from Walker 256 rat mammary tumor tissue demonstrated that this tumor tRNA almost totally lacks the hypermodified nucleosides Q and Q*. In addition, we have found that at least the major species of rat liver tRNA Asn contains the Q nucleoside. These studies indicate that chromatography on the acylated DBAE-cellulose matrix, couple with the analytical ion-exchange chromatography of cyanogen bromide treated and untreated amino-acyl-tRNA can be a valuable technique for the determination of alterations in the Q (or Q*) nucleoside content of the tRNAs isolated from normal and tumor tissues.
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PMID:Chromatographic behavior of several mammalian tRNAs on acylated dihydroxyl-borate cellulose and Aminex A-28. 33 87

Queuosine (Q), found exclusively in the first position of the anticodons of tRNA(Asp), tRNA(Asn), tRNA(His) and tRNA(Tyr), is synthesized in eucaryotes by a base-for-base exchange of queuine, the base of Q, for guanine at tRNA position 34. This reaction is catalyzed by the enzyme tRNA-guanine transglycosylase (EC 2.4.2.29). We measured the specific release of queuine from Q-5'-phosphate (queuine salvage) and the extent of tRNA Q modification in 6 human tumors carried as xenografts in immune-deprived mice. Q-deficient tRNA was found in 3 of the tumors but it did not correlate with diminished queuine salvage. The low tRNA Q content of one tumor, the HxGC3 colon adenocarcinoma, prompted us to examine a HxGC3-derived cell line, GC3/M. GC3/M completely lacks Q in its tRNA and measurable tRNA-guanine transglycosylase activity; the first example of a higher eucaryotic cell which lacks this enzyme. Exposure of GC3/M cells to 5-azacytidine induces the transient appearance of Q-positive tRNA. This result suggests that at least one allele of the transglycosylase gene in GC3/M cells may have been inactivated by DNA methylation. In clinical samples, we found Q-deficient tRNA in 10 of 46 solid tumors, including 2 of 13 colonic carcinomas.
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PMID:Absence of tRNA-guanine transglycosylase in a human colon adenocarcinoma cell line. 137 4

Changes in the glycosylation of asparagine-linked oligosaccharides have been shown in various tumor cells, including human colon cancer. Attempts were made to elucidate the difference in Asn-linked oligo-saccharides attached to lysosomal membrane glycoproteins isolated from sublines of human colon carcinoma exhibiting high and low metastatic potentials in nude mice. Lysosomal membrane glycoproteins (lamp) 1 and 2 were immunoprecipitated from the cells after labeling with radioactive sugars, and the glycopeptides prepared were fractionated by serial lectin affinity chromatography employing immobilized concanavalin A, Datura stramonium agglutinin, and tomato lectin. Comparison of Asn-linked oligosaccharides from the different colonic carcinoma cells revealed the following features. First, the highly metastatic carcinoma cells express more poly-N-acetyllactosaminyl side chains with branched galactose residues than cells with low metastatic potential. Second, sialylation is more significant in the highly metastatic carcinoma cells than in the poorly metastatic ones. Conversely, N-acetyllactosamine units are less fucosylated in the highly metastatic cells than in poorly metastatic cells. These structural changes were apparently caused by the increase in sialyltransferase and the decrease in alpha 1----3 fucosyltransferase in the highly metastatic cells. The results also suggest that highly metastatic carcinoma cells express more sialyl Lex structures at the termini of poly-N-acetyllactosaminyl side chains than poorly metastatic carcinoma cells. Further, highly metastatic cells were found to express more lamp-1 and lamp-2 on the cell surface. These results were found to be correlated to the increased expression of sialyl Lex structures with high affinity binding of anti-sialyl Lex antibody on highly metastatic cells. Increased expression of sialyl Lex in the poly-N-acetyllactosamines of the cell surface may contribute to the metastatic behavior of the cells, assuming that this structure can serve as a better ligand for selectins present on endothelial cells and platelets.
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PMID:Differential glycosylation and cell surface expression of lysosomal membrane glycoproteins in sublines of a human colon cancer exhibiting distinct metastatic potentials. 154 42

Translation initiation factor eIF-4E, which binds to the 5' cap structure of eukaryotic mRNAs, is believed to play an important role in the control of cell growth. Consistent with this, overexpression of eIF-4E in fibroblasts results in their malignant transformation. The activity of eIF-4E is thought to be regulated by phosphorylation on a single serine residue (Ser-53). Treatment of rat pheochromocytoma (PC12) cells with nerve growth factor (NGF) strongly curtails their growth and causes their differentiation into cells that resemble sympathetic neurons. The present study shows that eIF-4E is rapidly phosphorylated in PC12 cells upon NGF treatment, resulting in a significant increase in the steady-state levels of the phosphorylated protein. In contrast, epidermal growth factor, a factor which elicits a weak mitogenic response in PC12 cells, did not significantly enhance eIF-4E phosphorylation. We also show that although the mitogen and tumor promoter, phorbol 12-myristate-13-acetate, is able to induce phosphorylation of eIF-4E in PC12 cells, the NGF-mediated increase is primarily a protein kinase C-independent response. The NGF-induced enhancement of eIF-4E phosphorylation is abrogated in PC12 cells expressing a dominant inhibitory ras mutant (Ser-17 replaced by Asn), indicating that eIF-4E phosphorylation is dependent on a ras signalling pathway. As phosphorylation of eIF-4E effects translation initiation, these results suggest that NGF-mediated and ras-dependent eIF-4E phosphorylation may play a role in switching the pattern of gene expression during the differentiation of PC12 cells.
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PMID:Phosphorylation of translation initiation factor eIF-4E is induced in a ras-dependent manner during nerve growth factor-mediated PC12 cell differentiation. 154 5

Eight neutralizing monoclonal antibodies (mAbs) directed against the human interferon gamma (HuIFN-gamma) that were classified in the E1 epitope group were mapped by the synthetic peptide approach. A set of 136 octapeptide homologs of the 143-residue primary sequence of the HuIFN-gamma, each one with a 7-residue sequence overlap with successive peptide, was synthesized. Based on the similar reactivity patterns of all the mAbs with this set of synthetic peptides, the E1 functional epitope was localized to residues 84-94 on the HuIFN-gamma. The epitope sequence is: Ser-Asn-Lys-Lys-Lys-Arg-Asp-Asp-Phe-Gln-Lys. The fact that eight independently isolated mAbs binding to the same domain can neutralize the HuIFN-gamma activity suggests that the E1 domain must be at or adjacent to a functional site. Within this domain is a sequence element, Lys-Lys-Lys-Arg, that resembles the nuclear location signals known to effect the intracellular transportation of a number of nuclear proteins, such as the large tumor antigen (T antigen) of simian virus 40 (SV40) and polyoma virus and steroid hormone receptors. This observation suggests that the HuIFN-gamma molecule and/or its complex with the receptor must function in the nucleus to effect transcription regulation that results in the various biological activities. The signal for that intracellular transportation must be provided by the HuIFN-gamma molecule.
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PMID:The E1 functional epitope of the human interferon gamma is a nuclear targeting signal-like element. Mapping of the E1 epitope. 170 9

Identification of the G1-P120 antigen with the aid of the monoclonal antibody to its "human-specific epitope" has resulted in rapid development of information on its molecular biology. With the monoclonal antibody, it rapidly became possible to identify and subsequently sequence its cDNA and with cDNA clones to isolate and sequence its genomic DNA. It was demonstrated that the protein had 4 major domains: a basic domain, an acidic domain, a hydrophobic and methionine-rich domain and a domain rich in cysteine and proline residues. In addition to a nuclear recognition signal, the epitope region is juxtaposed to phosphorylation sites. The epitope region contains the sequence Gln-Ala-Ala-Ala-Gly-Ile-Asn-Trp which is unique to the human P120 molecule; this may be a site for drug attack either by analogs to the region or by novel constructs based on antisense oligonucleotides. When tumor cells were transfected with antisense constructs of the P120 gene, growth rates were markedly reduced. 3T3 cells transformed by transfection with the P120 gene reverted to a nontransformed state by subsequent transfection and activation of a P120 antisense construct. Opportunities for control of malignant cells with antisense oligonucleotides are currently under study.
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PMID:Nucleolar protein P120 and its targeting for cancer chemotherapy. 180 2

Malignant transformation of rodent cell lines by polyoma virus and by activated ras genes is associated with increased UDP-GlcNAc:Man alpha-R beta-1,6-N-acetylglucosaminyltransferase V (GlcNAc-transferase V) activity and it product -GlcNAc beta 1-6Man alpha 1-6Man beta 1-branched Asn-linked oligosaccharides. In this report, we have compared beta 1-6GlcNAc branching of core O- and N-linked oligosaccharides in three experimental models of malignancy, namely (a) rat2 fibroblasts and their malignant T24H-ras-transfected counterpart; (b) benign SP1 mammary carcinoma cells and two metastic sublines of SP1; and (c) the metastatic MDAY-D2 lymphoma cell line and its poorly metastatic glycosylation mutant KBL-1. In addition to the previously reported increase in GlcNAc-transferase V activity, UDP-GlcNAc:Gal beta 1-3GalNAc alpha-R (GlcNAc to GalNAc) beta-1,6-N-acetylglucosaminyltransferase (core 2 GlcNAc-transferase, EC 2.4.1.102) activity was found to be elevated by 70% in the malignant rat2 and SP1 cell lines while several other glycosyltransferase activities were not significantly different. The action of core 2 GlcNAc-transferase followed by beta 1-4Gal-transferase provides an N-acetyllactosamine antenna that can be extended with polylactosamine (i.e. repeating Gal beta 1-4GlcNAc beta 1-3) provided UDP-GlcNAc:Gal beta-R beta 1-3GlcNAc-transferase (GlcNAc-transferase) (i)) activity is present. Polylactosamine content in microsomal membrane glycoproteins was quantitated by labeling the GlcNAc termini resulting from the action of Escherichia freundii endo-beta-galactosidase with bovine galactosyltransferase/UDP-[3H] Gal. Glycopeptidase F- sensitive and -insensitive fractions were measured to assess the N- and O-linked components. In the SP1 tumor model, the metastatic sublines showed increased core 2 GlcNAc-transferase and GlcNAc-transferase V activities but no change in GlcNAc-transferase (i) activity, yet polylactosamine was increased in both O- and N-linked oligosaccharides. In rat2 cells, down-regulation of GlcNAc-transferase (i) following transformation was associated with decreased polyactosamine even though core 2 GlcNAc-transferase and GlcNAc-transferase V were elevated in the cells. Finally, a 3-fold decrease in GlcNAc-transferase V in KBL-1, the glycosylation mutant of MDAY-D2 cells, resulted in complete loss of polylactosamine in N-linked but no change in O-linked polylactosamine content. These results suggest that, provided GlcNAc-transferase (i) is not limiting, the beta 1-6-branching enzymes core 2 GlcNAc-transferase and GlcNAc-transferase V regulate the levels of polyactosamine in O- and N-linked oligosaccharides, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Increased UDP-GlcNAc:Gal beta 1-3GaLNAc-R (GlcNAc to GaLNAc) beta-1, 6-N-acetylglucosaminyltransferase activity in metastatic murine tumor cell lines. Control of polylactosamine synthesis. 182 44

Rana pipiens oocytes and early embryos contain large amounts of a basic protein with antiproliferative/cytotoxic activity against several tumor cell lines in vitro (Darzynkiewicz, Z., Carter, S. P., Mikulski, S. M., Ardelt, W., and Shogen, K. (1988) Cell Tissue Kinet. 21, 169-182; Mikulski, S.M., Viera, A., Ardelt, W., Menduke, H., and Shogen, K. (1990) Cell Tissue Kinet. 23, 237-246), as well as antitumor activity in vivo (Mikulski, S. M., Ardelt, W., Shogen, K., Bernstein, E. H., and Menduke, H. (1990) J. Natl. Cancer Inst. 82, 151-153). The protein, provisionally named P-30 Protein, was purified to homogeneity from early embryos and characterized. It is a single-chain protein consisting of 104 amino acid residues in the following sequence: less than Glu1-Asp-Trp-Leu-Thr-Phe-Gln-Lys-Lys-His-Ile-Thr-Asn-Thr- Arg15-Asp-Val-Asp-Cys-Asp-Ans-Ile-Met-Ser-Thr-Asn-Leu-Phe-His-C ys30-Lys-Asp-Lys - Asn-Thr-Phe-Ile-Tyr-Ser-Arg-Pro-Glu-Pro-Val-Lys45-Ala-Ile-Cys-Lys- Gly-Ile-Ile- Ala-Ser-Lys-Asn-Val-Leu-Thr-Thr60-Ser-Glu-Phe-Tyr-Leu-Ser-Asp -Cys-Asn-Val-Thr-Ser-Arg-Por-Cys75-Lys-Tyr-Lys-Leu-Lys-Lys-Ser-Thr -Asn-Lys-Phe- Cys-Val-Thr-Cys90-Glu-Asn-Gln-Ala-Pro-Val-His-Phe-Val-Gly-Val-Gly- Ser-Cys104-OH . Its molecular weight calculated from the sequence is 11,819. The sequence homology clearly indicates that the protein belongs to the superfamily of pancreatic ribonuclease. It is also demonstrated that it indeed exhibits a ribonucleolytic activity against highly polymerized RNA and that this activity seems to be essential for its antiproliferative/cytotoxic effects.
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PMID:Amino acid sequence of an anti-tumor protein from Rana pipiens oocytes and early embryos. Homology to pancreatic ribonucleases. 198 96

Chemical cross-linking and gel permeation chromatography were used to examine early events in the biogenesis of class I histocompatibility molecules. We show that newly synthesized class I heavy chains associate rapidly and quantitatively with an 88-kD protein in three murine tumor cell lines. This protein (p88) does not appear to possess Asn-linked glycans and it is not the abundant ER protein, GRP94. The class I-p88 complex exists transiently (t1/2 = 20-45 min depending on the specific class I heavy chain) and several lines of evidence suggest that p88 dissociates from the complex while still in the ER. Dissociation is not triggered upon binding of beta 2-microglobulin to the heavy chain (t1/2 = 2-5 min). However, the rate of dissociation does correlate with the characteristic rate of ER to Golgi transport for the particular class I molecule studied. Consequently, dissociation of p88 may be rate limiting for ER to Golgi transport. Class I molecules bind antigenic peptides, apparently in the ER, for subsequent presentation to cytotoxic T lymphocytes at the cell surface. p88 could promote peptide binding or it may retain class I molecules in the ER during formation of the ternary complex of heavy chain, beta 2-microglobulin, and peptide.
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PMID:Participation of a novel 88-kD protein in the biogenesis of murine class I histocompatibility molecules. 199 67


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