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Congenital diseases caused by defective O-glycosylation of Notch receptors Tashima, Yuko Okajima, Tetsuya open access Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Notch receptor O-glycosylation epidermal growth factor-like repeat EGF domain-specific O-GlcNAc transferase Adams-Oliver syndrome 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. Nagoya University Graduate School of Medicine, School of Medicine 2018-08 eng departmental bulletin paper VoR https://doi.org/10.18999/nagjms.80.3.299 http://hdl.handle.net/2237/00028523 https://nagoya.repo.nii.ac.jp/records/26320 10.18999/nagjms.80.3.299 http://www.med.nagoya-u.ac.jp/medlib/nagoya_j_med_sci/803.html 2186-3326 0027-7622 Nagoya Journal of Medical Science 80 3 299 307 https://nagoya.repo.nii.ac.jp/record/26320/files/02_Tashima.pdf application/pdf 446.1 kB 2018-08-28