@article{219b1b09b0084b39ac33c42e10ddd0eb,
title = "O-GlcNAc on NOTCH1 EGF repeats regulates ligand-induced Notch signaling and vascular development in mammals",
abstract = "The glycosyltransferase EOGT transfers O-GlcNAc to a consensus site in epidermal growth factor-like (EGF) repeats of a limited number of secreted and membrane proteins, including Notch receptors. In EOGT-deficient cells, the binding of DLL1 and DLL4, but not JAG1, canonical Notch ligands was reduced, and ligand-induced Notch signaling was impaired. Mutagenesis of O-GlcNAc sites on NOTCH1 also resulted in decreased binding of DLL4. EOGT functions were investigated in retinal angiogenesis that depends on Notch signaling. Global or endothelial cell-specific deletion of Eogt resulted in defective retinal angiogenesis, with a mild phenotype similar to that caused by reduced Notch signaling in retina. Combined deficiency of different Notch1 mutant alleles exacerbated the abnormalities in Eogt/ retina, and Notch target gene expression was decreased in Eogt/ endothelial cells. Thus, O-GlcNAc on EGF repeats of Notch receptors mediates ligand-induced Notch signaling required in endothelial cells for optimal vascular development.",
author = "Shogo Sawaguchi and Shweta Varshney and Mitsutaka Ogawa and Yuta Sakaidani and Hirokazu Yagi and Kyosuke Takeshita and Toyoaki Murohara and Koichi Kato and Subha Sundaram and Pamela Stanley and Tetsuya Okajima",
note = "Funding Information: We thank T Honjo for providing Rbpj mice, M Yanagisawa and RIKEN BioResource Center for providing Tek-Cre mice, K Uchimura for collaborative work, N Hattori for technical assistance, K Furukawa for supporting and supervising the project, M Nakakura and T Kawai for experiments in the initial phase of the project. Japan Society for the Promotion of ScienceJP15K15064 Mitsutaka Ogawa Tetsuya Okajima Takeda Science Foundation Tetsuya Okajima Japan Foundation for Applied Enzymology Tetsuya Okajima National Institutes of HealthRO1 GM106417 Pamela Stanley Japan Society for the Promotion of ScienceJP26110709 Tetsuya Okajima Japan Society for the Promotion of Science JP26291020 Kyosuke Takeshita Tetsuya Okajima Japan Society for the Promotion of Science JP15K18502 Mitsutaka Ogawa Japan Society for the Promotion of Science JP16J00004 Mitsutaka Ogawa Japan Society for the Promotion of Science JP15K07935 Hirokazu Yagi Japan Society for the Promotion of Science JP26110716 Hirokazu Yagi Japan Society for the Promotion of Science JP25102008 Koichi Kato The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: {\textcopyright} Sawaguchi et al.",
year = "2017",
month = apr,
day = "11",
doi = "10.7554/eLife.24419",
language = "English (US)",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}