The bisecting GlcNAc in cell growth control and tumor progression

Hazuki E. Miwa, Yinghui Song, Richard Alvarez, Richard D. Cummings, Pamela Stanley

Research output: Contribution to journalArticle

44 Scopus citations

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 Nglycans. 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.

Original languageEnglish (US)
Pages (from-to)609-618
Number of pages10
JournalGlycoconjugate Journal
Volume29
Issue number8-9
DOIs
StatePublished - Dec 1 2012

Keywords

  • Bisecting GlcNAc
  • Complex N-glycans
  • Galectins
  • Glycosylation
  • Mgat3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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