title: The bisecting GlcNAc in cell growth control and tumor progression.
abstract: The bisecting GlcNAc is transferred to the core mannose residue of complex or hybrid N-glycans on glycoproteins by the β1,4-N-acetylglucosaminyltransferase III (GlcNAcT-III) or MGAT3. The addition of the bisecting GlcNAc confers unique lectin recognition properties to N-glycans. Thus, LEC10 gain-of-function Chinese hamster ovary (CHO) cells selected for the acquisition of ricin resistance, carry N-glycans with a bisecting GlcNAc, which enhances the binding of the erythroagglutinin E-PHA, but reduces the binding of ricin and galectins-1, -3 and -8. The altered interaction with galactose-binding lectins suggests that the bisecting GlcNAc affects N-glycan conformation. LEC10 mutants expressing polyoma middle T antigen (PyMT) exhibit reduced growth factor signaling. Furthermore, PyMT-induced mammary tumors lacking MGAT3, progress more rapidly than tumors with the bisecting GlcNAc on N-glycans of cell surface glycoproteins. In recent years, evidence for a new paradigm of cell growth control has emerged involving regulation of cell surface residency of growth factor and cytokine receptors via interactions and cross-linking of their branched N-glycans with a lattice of galectin(s). Specific cross-linking of glycoprotein receptors in the lattice regulates their endocytosis, leading to effects on growth factor-induced signaling. This review will describe evidence that the bisecting GlcNAc of N-glycans regulates cellular signaling and tumor progression, apparently through modulating N-glycan/galectin interactions.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10461, USA.
authors.forename: Hazuki E
authors.initials: HE
authors.lastname: Miwa
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Song
authors.forename: Richard
authors.initials: R
authors.lastname: Alvarez
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
authors.forename: Pamela
authors.initials: P
authors.lastname: Stanley
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D018450:Disease Progression; D037161:Galectins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D037161:Galectins; D036341:Intercellular Signaling Peptides and Proteins; D017351:N-Acetylglucosaminyltransferases; D000117:Acetylglucosamine