Two novel protein O -glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling

This is the authors' abstract. We don't add key points for this paper.

Significance The Notch-signaling pathway is normally activated by receptor–ligand interactions. Extracellular domains (ECDs) of Notch receptors are heavily modified with O -linked glycans, such as O -glucose ( O -Glc), O -fucose ( O -Fuc), and O -GlcNAc. The significance of multiple types of O -glycans on Notch is not understood. NOTCH1 ECD interacts with ligands at multiple points, including an O -Glc monosaccharide on the 11th Epidermal Growth Factor (EGF) repeat (EGF11). Here, we identify two novel protein O -glucosyltransferases that modify NOTCH1 EGF11 with O -Glc. Combined deletion of the O -Glc site on EGF11 with O -Fuc modification sites on EGF8 or EGF12 markedly reduced NOTCH1 cell-surface expression or activation of NOTCH1 by Delta-like ligand 1, respectively. This study identifies a cooperative mechanism for fine-tuning the Notch-signaling pathway by different types of O -glycans.