Congenital diseases caused by defective O-glycosylation of Notch receptors
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Abstract
The Notch signaling pathway is highly conserved and essential for animal development. It is required for cell differentiation, survival, and proliferation. Regulation of Notch signaling is a crucial process for human health. Ligands initiate a signal cascade by binding to Notch receptors expressed on a neighboring cell. Notch receptors interact with ligands through their epidermal growth factor-like repeats (EGF repeats). Most EGF repeats are modified by O-glycosylation with residues such as O-linked N-acetylglucosamine (O-GlcNAc), O-fucose, and O-glucose. These O-glycan modifications are important for Notch function. Defects in O-glycosylation affect Notch-ligand interaction, trafficking of Notch receptors, and Notch stability on the cell surface. Although the roles of each modification are not fully understood, O-fucose is essential for binding of Notch receptors to their ligands. We reported an EGF domain-specific O-GlcNAc transferase (EOGT) localized in the endoplasmic reticulum. Mutations in genes encoding EOGT or NOTCH1 cause Adams-Oliver syndrome. Dysregulation of Notch signaling because of defects or mutations in Notch receptors or Notch signal-regulating proteins, such as glycosyltransferases, induce a variety of congenital disorders. In this review, we discuss O-glycosylation of Notch receptors and congenital human diseases caused by defects in O-glycans on Notch receptors.
Journal
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- Nagoya Journal of Medical Science
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Nagoya Journal of Medical Science 80 (3), 299-307, 2018-08
Nagoya University Graduate School of Medicine, School of Medicine
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Details 詳細情報について
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- CRID
- 1390290699599937024
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- NII Article ID
- 120006502463
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- ISSN
- 21863326
- 00277622
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- HANDLE
- 2237/00028523
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- Text Lang
- en
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- Data Source
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- JaLC
- IRDB
- CiNii Articles
- KAKEN
- Crossref
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- Abstract License Flag
- Allowed