Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1780, Issue 3, Pages 546-563Publisher
ELSEVIER
DOI: 10.1016/j.bbagen.2007.09.010
Keywords
mucin-type O-glycosylation; glycosyltransferases; mucins; site-directed O-glycosylation; GaINAc-transferases; cancer vaccines
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Mucin-type O-glycans are found on mucins as well as many other glycoproteins. The initiation step in synthesis is catalyzed by a large family of polypeptide Ga1NAc-transferases attaching the first carbohydrate residue, Ga1NAc, to selected serine and threonine residues in proteins. During the last decade an increasing number of Ga1NAc-transferase isoforms have been cloned and their substrate-specificities partly characterized. These differences in substrate specificities have been exploited for in vitro site-directed O-glycosylation. In GlycoPEGylation((TM)), polyehylene glycol (PEG) is transferred to recombinant therapeutics to specific acceptor sites directed by GaINAc-transferases. GaINAc-transferases have also been used to control density of glycosylation in the development of glycopeptide-based cancer vaccines. The membrane-associated mucin-1 (MUC1) has long been considered a target for immunotherapeutic and immunodiagnostic measures, since it is highly overexpressed and aberrantly O-glycosylated in most adenocarcinomas, including breast, ovarian, and pancreatic cancers. By using vaccines mimicking the glycosylation pattern of cancer-cells, it is possible to overcome tolerance in transgenic animals expressing the human MUC1 protein as a self-antigen providing important clues for an improved MUC1 vaccine design. The present review will highlight some of the potential applications of site-directed O-glycosylation. (C) 2007 Elsevier B.V. All rights reserved.
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