Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of carbohydrate antigens has been shown by retrospective immunohistochemical analysis to correlate to the progression and metastases of human cancers. However, the mechanisms of these changes of carbohydrate expression and the role of carbohydrates in the malignant behavior of tumor cells are not well known. In this article, we introduce methods to experimentally modify carbohydrate expression in tumor cells and to assess the involvement of these carbohydrate antigens in the malignant behavior of tumor cells. Modifications of the biosynthesis of O- and N-linked carbohydrates, and glycolipids are achieved by treating cultured tumor cells with culture media containing Benzyl-alpha-GalNAc, swainsonine, or D-PDMP, respectively. Enzymatic digestion of cell surface carbohydrates with sialidase, endo-beta-galactosidase or other glycosidases can also be performed. These cells can be used for short term experiments such as adhesion assays. However, modified carbohydrates may be recovered during in vitro and in vivo assays. By transfection of glycosyltransferase cDNA, or selection of tumor cells by binding lectins or antibodies, stable carbohydrate variant cells can be obtained which are suitable for long term experiments such as the experimental formation of metastases in vivo. The biological function of tumor cell surface carbohydrates may be diverse. These molecules are thought to influence adhesion interaction between tumor cells and the endothelial cells of target organs. However, carbohydrate recognition molecules, or lectins, are expressed on a variety of cells in the vascular system and in the immune system. Therefore, it is essential to design appropriate experimental models to study the biological significance of carbohydrate-lectin interactions in cancer progression and metastatic dissemination. Adhesion assays of tumor cells to selectin-transfected CHO cells were performed. Taking molecules other than selectins into consideration, adhesion assays using frozen tissue sections were also performed.
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PMID:[Tumor metastases and adhesion molecules carbohydrates and lectins]. 1041 Jan 58

Adhesion of Streptococcus parasanguinis to saliva-coated hydroxyapatite (SHA), an in vitro tooth model, is mediated by long peritrichous fimbriae. Fap1, a fimbria-associated serine-rich glycoprotein, is required for fimbrial assembly. Biogenesis of Fap1 is controlled by an 11-gene cluster that contains gly, nss, galT1 and -2, secY2, gap1 to -3, secA2, and gtf1 and -2. We had previously isolated a collection of nine nonadherent mutants using random chemical mutagenesis approaches. These mutants fail to adhere to the in vitro tooth model and to form fimbriae. In this report, we further characterized these randomly selected nonadherent mutants and classified them into three distinct groups. Two groups of genes were previously implicated in Fap1 biogenesis. One group has a mutation in a glycosyltransferase gene, gtf1, that is essential for the first step of Fap1 glycosylation, whereas the other group has defects in the fap1 structural gene. The third group mutant produces an incompletely glycosylated Fap1 and exhibits a mutant phenotype similar to that of a glycosylation-associated protein 1 (Gap1) mutant. Analysis of this new mutant revealed that a conserved C-terminal 13-amino-acid motif was missing in Gap1. Site-directed mutagenesis of a highly conserved amino acid tryptophan within this motif recapitulated the deletion phenotype, demonstrating the importance of the Gap1 C-terminal motif for Fap1 biogenesis. Furthermore, the C-terminal mutation does not affect Gap1-Gap3 protein-protein interaction, which has been shown to mediate Fap1 glycosylation, suggesting the C-terminal motif has a distinct function related to Fap1 biogenesis.
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PMID:A conserved C-terminal 13-amino-acid motif of Gap1 is required for Gap1 function and necessary for the biogenesis of a serine-rich glycoprotein of Streptococcus parasanguinis. 1885 49

Nontypeable Haemophilus influenzae (NTHi) is a leading cause of respiratory tract infections worldwide and continues to be a global health burden. Adhesion and colonization of host cells are crucial steps in bacterial pathogenesis, and in many strains of NTHi, the interaction with the host is mediated by the high molecular weight adhesins HMW1A and HMW2A. These adhesins are N-glycoproteins that are modified by cytoplasmic glycosyltransferases HMW1C and HMW2C. Phase variation in the number of short sequence repeats in the promoters of hmw1A and hmw2A directly affects their expression. Here, we report the presence of similar variable repeat elements in the promoters of hmw1C and hmw2C in diverse NTHi isolates. In an ex vivo assay, we systematically altered the substrate and glycosyltransferase expression and showed that both of these factors quantitatively affected the site-specific efficiency of glycosylation on HMW-A. This represents a novel mechanism through which phase variation can generate diversity in the quantitative extent of site-specific post-translational modifications on antigenic surface proteins. Glycosylation occupancy was incomplete at many sites, variable between sites, and generally lower close to the C-terminus of HMW-A. We investigated the causes of this variability. As HMW-C glycosylates HMW-A in the cytoplasm, we tested how secretion affected glycosylation on HMW-A and showed that retaining HMW-A in the cytoplasm indeed increased glycosylation occupancy across the full length of the protein. Site-directed mutagenesis showed that HMW-C had no inherent preference for glycosylating asparagines in NxS or NxT sequons. This work provides key insights into factors contributing to the heterogenous modifications of NTHi HMW-A adhesins, expands knowledge of NTHi population diversity and pathogenic capability, and is relevant to vaccine design for NTHi and related pathogens.
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PMID:Phase-Variable Glycosylation in Nontypeable Haemophilus influenzae. 3177 88