UMLS:C0027819 - FACTA Search

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

Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A glycoprotein, M(r) 200,000, which has the biological activity of the neurotoxin-responsive Na+ channel, was isolated from a clonal line of mouse neuroblastoma cells, N-18. The glycoprotein was purified to homogeneity in 18% yield by methods used to purify glycoproteins, which included metabolic labeling of the cells with L-[3H]fucose and binding of the radioactive glycoproteins to WGA- and lentil-Sepharose, and DEAE-cellulose. The glycoprotein has biological activity of neurotoxin-responsive ion flux when reconstituted into artificial phospholipid vesicles. This activity was shown to depend on the presence of sialic acid since treatment of the purified, reconstituted glycoprotein with Vibrio cholerae neuraminidase abolished the response to neurotoxins of 86Rb flux. The [3H]fucose-containing glycopeptides derived by Pronase digestion of the glycoprotein were characterized by affinity to immobilized lectins and contained di-, tri-, and tetra-antennary oligosaccharides in a ratio of 2:4:3. Most of the glycopeptides were sialylated as shown by binding characteristics to immobilized serotonin-Sepharose with and without neuraminidase. The structure of the diantennary oligosaccharides was elucidated by 500-MHz 1H NMR spectroscopy. The Con A-bound fraction contains alpha-NeuNAc-(2-->6)-bound group on the GlcNAc5' antenna and an alpha-NeuNAc-(2-->3)-bound groups on the GlcNAc5 antenna. An alpha-L-fucosyl group is (1-->6)-bound to the Asn core GlcNAc1 residue.
...
PMID:Oligosaccharide composition of the neurotoxin-responsive sodium channel of mouse neuroblastoma and requirement of sialic acid for biological activity. 133 66

Loss of heterozygosity (LOH) on chromosome 18q21 is found frequently in various human cancers. Three candidate tumor suppressor genes, DCC (deleted in colorectal carcinomas), DPC4 (deleted in pancreatic carcinomas, locus 4), and MADR2/JV18-1 (MAD-related gene 2), have been cloned and identified from this chromosome region. We have reported recently that LOH on chromosome 18q is observed frequently in neuroblastoma. Alterations of DCC are involved in many human tumors. DPC4 and MADR2/JV18-1 are recently demonstrated to be altered in pancreatic and colorectal cancers, respectively. To confirm if inactivation of the DCC, DPC4, and MADR2/JV18-1 genes is involved in the pathogenesis of neuroblastoma and to clarify the mechanism of inactivation, we analyzed the expression of DCC, DPC4, and MADR2/JV18-1 in neuroblastoma cell lines and primary tumors by reverse transcription-PCR and investigated the mutations in the coding regions of these genes by PCR/reverse transcription-PCR single-strand conformation polymorphism. We found that 12 of 25 (48%) cell lines and 14 of 32 (44%) primary tumors, including 3 with 18q LOH, had absent or reduced expression of DCC mRNA. Expression was more likely to be reduced in advanced (67%) than in early stage neuroblastomas (24%) (P = 0.036), suggesting that inactivation of the DCC gene plays an important role in the progression of neuroblastoma. Altered expression of DPC4 was found in six (24%) cell lines and six (19%) tumors. MADR2/JV18-1 expression was reduced or absent only in four (16%) cell lines and three (9%) tumors. Mutations of the DCC genes were examined in 25 of 29 exons in neuroblastoma cell lines, and those exons in which mutations were found were further examined in primary tumors. We found missense mutations of AAC (Asn) to AGC (Ser) at DCC codon 176 in one cell line and ACC (Thr) to ATC (Ile) at codon 1105 in one cell line and tumor, respectively; polymorphisms of CGA (Arg) to GGA (Gly) at codon 201 and TTT (Phe) to TTG (Leu) at codon 951 in most of the cell lines and tumors; and a silent mutation of GAG (Glu) to GAA (Glu) at codon 118 in four cell lines and five primary tumors. We did not identify any mutations in the DPC4 and MADR2/JV18-1 genes in neuroblastoma. Our results suggested that mutations of the DCC gene may be involved in the pathogenesis of neuroblastomas but failed to account for the relatively high frequency of the altered expression, implying that other mechanisms are responsible for the inactivation of the DCC gene in neuroblastoma. Low frequency of reduced or absent mRNA expression and lack of mutations in DPC4 and MADR2/JV18-1 genes suggested a limited role for these two genes in neuroblastoma.
...
PMID:Expression and mutational analysis of the DCC, DPC4, and MADR2/JV18-1 genes in neuroblastoma. 928 86

After 2.5 months of persistent infection in human neuroblastoma cells by the type 3 poliovirus (PV3) wild-type Leon strain, a mutant (PVpi), L2-2, capable of establishing a persistent infection in nonneural HEp-2c cells was isolated. Sequence analysis of the viral capsid protein genes revealed the presence of seven missense mutations, three of which were also present in a second PVpi, suggesting that they could be important determinants of the persistent phenotype. When the three mutations were introduced into the lytic Leon strain separately, in pairs or all together, all but one of the viruses was capable of establishing a persistent infection. However, aside from the triple mutant, only one mutant virus, bearing a Leu at position VP213 in the capsid interior and an Asn at position VP1290 on the capsid surface, was capable of establishing persistent infections in more than 30% of the cultures. When present together, these two determinants affect the early steps of the virus cycle including cell binding and the receptor-mediated conformational changes believed to be necessary for viral penetration and uncoating. In fact, this persistent double mutant appears to undergo a novel capsid transition when in contact with the human PV receptor, altering from the native virion which sediments at 160S to a form which sediments at about 147S. We propose that this modification could be the mechanism by which PV3 is able to establish persistent infections in HEp-2c cell cultures.
...
PMID:Two amino acid substitutions in the type 3 poliovirus capsid contribute to the establishment of persistent infection in HEp-2c cells by modifying virus-receptor interactions. 945 13

Alanyl aminopeptidase (AAP-S) was purified to homogeneity from rat liver cytosol. The molecular weight of the purified enzyme was calculated to be approximately 100,000 on Sephacryl S-200 HR and to be 90,000 on SDS-PAGE in the presence of beta-mercaptoethanol. These findings suggested that the enzyme exists as a monomeric form in rat liver cytosol. The enzyme rapidly hydrolyzed the substrates Ala-, Tyr- and Met-MCAs, and moderately hydrolyzed Arg-, Lys-, Leu-, Phe- and Lys-Ala-MCAs at pHs ranging from 7.5to 8.0. The enzyme also hydrolyzed several amino acid 4-methyl-coumaryl-7-amide (MCA) substrates. The order for k(cat)/Km values of AAP-S at the optimal pH (pH 7.5) was Lys->Met->Arg->Ala->Leu->Phe->Tyr->Lys-Ala-MCAs. It was strongly inhibited by bestatin, leuhistin, actinonin, amastatin, 1, 10-phenanthroline, PCMBS, Zn2+, Cd2+, Co2+, Cu2+ and Hg2+, and puromycin. The amino acid sequence of the first 43 residues of the enzyme was determined as Pro1-Glu-Lys-Arg-Pro5-Phe-Glu-Arg-Leu-Pro10-Thr-Glu-Val-Ser-Pro 15-Ile-Asn-Tyr-Ser-Leu20-(Cys)-Leu-Lys-Pro-Asp25-Leu-Leu- Asp-Phe-Thr30-Phe-Glu-Gly-Lys-Leu35-Glu-Ala-Ala-Ala-Gln40 -Val-Arg-Gln-. This N-terminal amino acid sequence is almost identical with those of puromycin-sensitive enkephalin-degrading aminopeptidases in rat and human brains, and the mouse neuroblastoma cell line Neuro2A. These findings suggest that the AAP-S from rat liver cytosol is a puromycin-sensitive aminopeptidase. Furthermore, with immunohistochemistry the enzyme was strongly stained in the cytosol of the rat liver cells.
...
PMID:Isolation and characterization of an alanyl aminopeptidase from rat liver cytosol as a puromycin-sensitive enkephalin-degrading aminopeptidase. 968 21

The vanilloid receptor VR1 is an ion channel predominantly expressed by primary sensory neurons involved in nociception. Here we describe its biochemical properties and assess the subcellular localization, the glycosylation state and the quaternary structure of VR1 expressed in HEK293 cells and in the DRG-derived cell line F-11 (N18TG2 mouse neuroblastoma x rat dorsal root ganglia, hybridoma). VR1 was found to be glycosylated in both cell types. Of the five potential N-glycosylation sites, the predicted transient receptor potential channel-like transmembrane folding proposes N604 is localized extracellularly. We used site-directed mutagenesis to mutate the Asn at position 604 to Thr. This mutated VR1 was not glycosylated, confirming the extracellular location of N604 and its role as the exclusive site of glycosylation of the VR1 protein. VR1 occured in high molecular mass complexes as assessed by blue native PAGE. In the presence of limited amounts of SDS dimers, trimers and tetramers of VR1 were observed, consistent with the predicted tetrameric quaternary structure of the receptor. Cross-linking with dimethyladipimidate yielded almost exclusively dimers. Whereas VR1 localized both to the plasma membrane and to intracellular membranes in HEK293 cells, it localized predominantly to the plasma membrane in F-11 cells. Using confocal laserscanning microscopy, we observed an enrichment of anti-VR1 immunoreactivity in neurite-like structures of F-11 cells. In the light of conflicting literature data on biochemical characteristics of VR1, our data suggest that dorsal root ganglion-derived F-11 cells provide a powerful experimental system for the study of VR1 biochemistry.
...
PMID:Biochemical characterization of the vanilloid receptor 1 expressed in a dorsal root ganglia derived cell line. 1168 72

Lectin from a leaf of Erythrina indica was isolated by affinity chromatography on Lactamyl-Seralose 4B. Lectin gave a single band in polyacrylamide gel electrophoresis (PAGE). In SDS-gel electrophoresis under reducing and non-reducing conditions Erythrina indica leaf lectin (EiLL) split into two bands with subunit molecular weights of 30 and 33 kDa, whereas 58 kDa was obtained for the intact lectin by gel filtration on Sephadex G-100. EiLL agglutinated all human RBC types, with a slight preference for the O blood group. Lectin was found to be a glycoprotein with a neutral sugar content of 9.5%. The carbohydrate specificity of lectin was directed towards D-galactose and its derivatives with pronounced preference for lactose. EiLL had pH optima at pH 7.0; above and below this pH lectin lost sugar-binding capability rapidly. Lectin showed broad temperature optima from 25 to 50 degrees C; however, at 55 degrees C EiLL lost more than 90% of its activity and at 60 degrees C it was totally inactivated. The pI of EiLL was found to be 7.6. The amino acid analysis of EiLL indicated that the lectin was rich in acidic as well as hydrophobic amino acids and totally lacked cysteine and methionine. The N-terminal amino acids were Val-Glu-Thr-IIe-Ser-Phe-Ser-Phe-Ser-Glu-Phe-Glu-Ala-Gly-Asn-Asp-X-Leu-Thr-Gln-Glu-Gly-Ala-Ala-Leu-. Chemical modification studies of both EiLL and Erythrina indica seed lectin (EiSL) with phenylglyoxal, DEP and DTNB revealed an absence of arginine, histidine and cysteine, respectively, in or near the ligand-binding site of both lectins. Modification of tyrosine with NAI led to partial inactivation of EiLL and EiSL; however, total inactivation was observed upon NBS-modification of two tryptophan residues in EiSL. Despite the apparent importance of these tryptophan residues for lectin activity they did not seem to have a direct role in binding haptenic sugar as D-galactose did not protect lectin from inactivation by NBS.
...
PMID:Purification, some properties of a D-galactose-binding leaf lectin from Erythrina indica and further characterization of seed lectin. 1250 84

In vitro transcription/translation studies with model proteins have shown that glycosylation of Asn-Xaa-Thr sequons is reduced when the sequon is within 60 residues of the C-terminus of the protein. We have previously shown that in living cells N-glycosylation of the prion protein (PrP) is also abolished when its Asn-Ile-Thr and Asn-Phe-Thr sequons are less than 60 residues from the C-terminus (Walmsley and Hooper [2003] Biochemical Journal, 370, 351-355). To investigate whether sequon distance to the C-terminus is a general determinant of N-glycosylation in living cells, Asn-Ile/Phe-Thr sequons were introduced into another glycosylphosphatidylinositol (GPI) anchored protein, membrane dipeptidase (MDP), at similar distances from the C-terminus as those in PrP. When expressed in the human neuroblastoma SH-SY5Y cell line, the introduced sequons were fully N-glycosylated even when they were less than 60 residues from the C-terminus in both GPI-anchored and secreted forms of MDP. These data demonstrate that the utilization of sequons in some proteins is independent of their distance from the C-terminus.
...
PMID:Glycosylation efficiency of Asn-Xaa-Thr sequons is independent of distance from the C-terminus in membrane dipeptidase. 1277 76

A yellow fever (YFV) 17D virus variant, which causes persistent infection of mouse neuroblastoma cells associated with defective cell penetration and small plaque size, yielded plaque-revertant viruses from cells transfected with viral transcripts encoding the adaptive mutation (Gly360 in the E protein). Reconstruction of a plaque-purified revertant which contained Gly360 and additional substitutions (Asn for Lys303 and Val for Ala261) yielded a virus whose infectious center size, growth efficiency, and cell penetration rate similar to the parental YF5.2iv virus, whereas viruses with Asn303 or Val261 alone with Gly360 yielded either a small-plaque virus or a parental revertant. These data indicate that the YFV E protein is subject to suppression of mutations in domain III that are deleterious for viral entry and spread by a second-site mutation in domain II. Position 261 lies within the hydrophobic ligand-binding pocket at the domain I-II interface, a site believed to be involved in the hinge-like conformational change of domain II during activation of membrane fusion-activity. Results of this study provide genetic data consistent with findings on flavivirus structure and implicate domain III in functions beyond simply cell surface attachment.
...
PMID:Yellow fever 17D virus: pseudo-revertant suppression of defective virus penetration and spread by mutations in domains II and III of the E protein. 1532 96

Human FGF19 is the ortholog of rodent Fgf15, and 22 FGF family genes exist within the human genome as well as within the rodent genome. Mouse Fgf11 refSeq NM_010198.1 and rat Fgf11 RefSeq NM_130816.1 correspond only to the coding region. Here, complete coding sequences of mouse, rat and dog Fgf11 orthologs were determined by using bioinformatics. Mouse Fgf11, rat Fgf11 and dog Fgf11 genes, consisting of five exons, were located within AL603707.5, AC098923.8 and AC126237.5 genome sequences, respectively. Human FGF11 showed 97.8%, 96.9%, 96.9% and 68.9% total-amino-acid identity with dog, mouse, rat and zebrafish Fgf11 orthologs, respectively. Rat Fgf11 showed Val205Met amino-acid substitution compared with rat Fgf11 RefSeq NP_570829.1. Met 205 of rat Fgf11 determined in this study was conserved among vertebrate Fgf11 orthologs. N-terminal signal peptide was not identified within vertebrate Fgf11 orthologs. Two Asn-linked glycosylation sites were identified within zebrafish fgf11, but not within mammalian Fgf11 orthologs. The 5'-flanking region, exonic regions, and intronic regions except intron 3 were well conserved between human FGF11 and mouse Fgf11 genes. Match program revealed that EVI1, ELK1, AP1 and E47-binding sites were conserved between human FGF11 and mouse Fgf11 promoter regions. Human FGF11 mRNA was expressed in embryonic stem (ES) cells, neuroblastoma, retinoblastoma, and brain tumors. This is the first report on the dog Fgf11 gene as well as on comparative genomics analyses of Fgf11 orthologs.
...
PMID:Comparative genomics on Fgf11 orthologs. 1594 3

alpha-mannosidase from Erythrina indica seeds is a Zn(2+) dependent glycoprotein with 8.6% carbohydrate. The enzyme has a temperature optimum of 50 degrees C and energy of activation calculated from Arrhenius plot was found to be 23 kJ mol(-1). N-terminal sequence up to five amino acid residues was found to be DTQEN (Asp, Thr, Gln, Glu, and Asn). In chemical modification studies treatment of the enzyme with NBS led to total loss of enzyme activity and modification of a single tryptophan residue led to inactivation. Fluorescence studies over a pH range of 3-8 have shown tryptophan residue to be in highly hydrophobic environment and pH change did not bring about any appreciable change in its environment. Far-UV CD spectrum indicated predominance of alpha-helical structure in the enzyme. alpha-Mannosidase from E indica exhibits immunological identity with alpha-mannosidase from Canavalia ensiformis but not with the same enzyme from Glycine max and Cicer arietinum. Incubation of E. indica seed lectin with alpha-mannosidase resulted in 35% increase in its activity, while no such activation was observed for acid phosphatase from E. indica. Lectin induced activation of alpha-mannosidase could be completely abolished in presence of lactose, a sugar specific for lectin.
...
PMID:Characterization of alpha-mannosidase from Erythrina indica seeds and influence of endogenous lectin on its activity. 1693 28

1 2 3 Next >>