https://scholars.lib.ntu.edu.tw/handle/123456789/143981
標題: | Enhanced expression of β3-galactosyltransferase 5 activity is sufficient to induce in vivo synthesis of extended type 1 chains on lactosylceramides of selected human colonic carcinoma cell lines | 作者: | Lin, Chi-Hung Fan, Yao-Yun Chen, Yen-Ying Wang, Shih-Hsin Chen, Chun-I Yu, Lung-Chih Khoo, Kay-Hooi |
關鍵字: | β3-galactosyltransferase; β3GalT5; Extended type 1 chain; Glycomics; Mass spectrometry | 公開日期: | 2009 | 卷: | 19 | 期: | 4 | 起(迄)頁: | 418-427 | 來源出版物: | Glycobiology | 摘要: | In general, an elevated expression of β3-galactosyltrans-ferase (β3GalT) activity contributed by β3GalT5 correlates well with increased biosynthesis and expression of type 1 chain (Galβ1-3GlcNAcβ1-) derivatives such as Lewis A and sialyl Lewis A, which are mostly recognized as terminal epitopes and not further extended. Most known β3-N-acetylglucosaminyltransferases show a higher activity toward extending type 2 chain (Galβ1-4GlcNAcβ1-), and an over-expression of β3GalT5 could suppress the formation of the type 2 chain poly-N- acetyllactosaminoglycans. The potential of extending instead the predominant type 1 chain termini synthesized under such circumstances was, however, not investigated, partly due to technical difficulty in unambiguous identification of extended type 1 chains. Using an advanced mass spectrometry-based glycomic mapping and glycan sequencing approach, we show here that type 1 chains carried on the lacto-series glycosphingolipids of colonic carcinoma cells can be extended when the endogenous β3GalT activity relative to competing β4GalT activity, as defined against a common GlcNAcβ1-3Galβ1-4Glc acceptor, is sufficiently high, as found in Colo205 and SW1116, but not in DLD-1 cells. In support of this positive correlation, the lacto-series glycosphingolipids isolated from stably transfected DLD-1 clones over-expressing β3GalT5 were shown to comprise fucosylated dimeric type 1 chains, whereas a mock transfectant and the DLD-1 parent carried only fucosylated dimeric type 2 chains on their lactosylceramides. It suggests that while the natural expression of extended type 1 chain is likely to be determined by many contributing factors including the relative amounts of competing glycosyltransferases and the UDP-Gal level, the enhanced expression of β3GalT5 is sufficient to promote in vivo extension of type 1 chains by furnishing a significantly higher amount of type 1 chain precursors relative to competing type 2 chains. ? The Author 2009. Published by Oxford University Press. All rights reserved. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/163317 | DOI: | 10.1093/glycob/cwn156 | SDG/關鍵字: | beta 3 galactosyltransferase 5; galactosyltransferase; glycosyltransferase; lactosylceramide; unclassified drug; uridine diphosphate galactose; article; cancer cell culture; cellular distribution; colon carcinoma; controlled study; enzyme activity; enzyme structure; gene overexpression; genetic variability; human; human cell; mass spectrometry; priority journal; protein analysis; protein determination; protein expression; protein synthesis; Antigens, CD; Carbohydrate Conformation; Cell Line, Tumor; Colonic Neoplasms; Galactosyltransferases; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Lactosylceramides; Mass Spectrometry; Oligosaccharides |
顯示於: | 生化科學研究所 |
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