원문정보
초록
영어
The use of glycan changes in their structure and function play pivotal roles in novel biomarker discovery and disease therapeutics. For example, regarding cancer biomarkers, fucosylated AFP and fucosylated haptoglobin are promising cancer biomarkers for hepatocarcinoma and pancreatic cancer, respectively. Deletion of core fucose from IgG1 molecule results in 100 fold activation of ADCC (antibody dependent cellular cytotoxicity) activity in antibody therapy. We have recently proposed the concept of the “glycan cycle” as a functional unit of glycans that will permit the integration of glycan functions in relation to diseases For example, glucose enters the cell via a glucose transporter and is converted to UDP-GlcNAc via the hexosamine pathway. UDP-GlcNAc plays a key role in the cytosol and is then incorporated into the Golgi via the UDPGlcNAc transporter and serves as a donor substrate for various GlcNAc-transferases from GnT-I to GnT-VI. UDP-GlcNAc also serves as a donor for O-GlcNAc-transferase in the cytosol. These enzymes function to modify target proteins such as TGF-beta, the EGFR, and the glucose transporter. These receptors are localized on the cell surface and bind to lectins such as galectin-3. When the affinity of lectin binding is decreased due to changes in receptor glycosylation, the receptors are endocytosed and degraded in acidic endosome/lysosome, and the free monosaccharide is probably recycled. This conceptual “functional unit of the glycan cycle,” such as just described for GlcNAc, is intended to help developing the understanding of the integrative and dynamic analysis of glycan functions.