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The bisecting GlcNAc in cell growth control and tumor progression

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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.

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Acknowledgments

The authors gratefully acknowledge the contribution of Dr. Santosh Patnaik in acquiring the data presented in Fig. 1c. This work was supported by R01 CA30645 and R01 CA36434 to PS, training grant T32 CA009173-34 to HEM, and by resources from the Consortium for Functional Glycomics (Core D and Core H) funded by NIGMS 1U54 GM62116.

Author information

Author notes

  1. Richard Alvarez

    Present address: Selexys Pharmaceuticals Corporation, 840 Research Parkway, Suite 510, Oklahoma City, OK, 73104, USA

  2. Richard D. Cummings

    Present address: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA

Authors and Affiliations

  1. Department of Cell Biology, Albert Einstein College of Medicine, New York, NY, 10461, USA

    Hazuki E. Miwa, Yinghui Song & Pamela Stanley

  2. Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Richard Alvarez & Richard D. Cummings

Authors
  1. Hazuki E. Miwa
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  2. Yinghui Song
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  3. Richard Alvarez
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  4. Richard D. Cummings
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  5. Pamela Stanley
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Correspondence to Pamela Stanley.

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Miwa, H.E., Song, Y., Alvarez, R. et al. The bisecting GlcNAc in cell growth control and tumor progression. Glycoconj J 29, 609–618 (2012). https://doi.org/10.1007/s10719-012-9373-6

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  • DOI: https://doi.org/10.1007/s10719-012-9373-6

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