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• W4226013670 abstract "N-Linked glycosylation and O-linked N-acetylglucosamine (O-GlcNAc) are important protein post-translational modifications that are orchestrated by a diverse set of gene products. Thus far, the relationship between these two types of glycosylation has remained elusive, and it is unclear whether one influences the other via UDP-GlcNAc, which is a common donor substrate. Theoretically, a decrease in O-GlcNAcylation may increase the products of GlcNAc-branched N-glycans. In this study, via examination by lectin blotting, HPLC, and mass spectrometry analysis, however, we found that the amounts of GlcNAc-branched tri-antennary N-glycans catalyzed by N-acetylglucosaminyltransferase IV (GnT-IV) and tetra-antennary N-glycans were significantly decreased in O-GlcNAc transferase knockdown cells (OGT-KD) compared with those in wild type cells. We examined this specific alteration by focusing on SLC35A3, which is the main UDP-GlcNAc transporter in mammals that is believed to modulate GnT-IV activation. It is interesting that a deficiency of SLC35A3 specifically leads to a decrease in the amounts of GlcNAc-branched tri- and tetra-antennary N-glycans. Furthermore, co-immunoprecipitation experiments have shown that SLC35A3 interacts with GnT-IV, but not with N-acetylglucosaminyltransferase V. Western blot and chemoenzymatic labeling assay have confirmed that OGT modifies SLC35A3 and that O-GlcNAcylation contributes to its stability. Furthermore, we found that SLC35A3-KO enhances cell spreading and suppresses both cell migration and cell proliferation, which is similar to the phenomena observed in the OGT-KD cells. Taken together, these data are the first to demonstrate that O-GlcNAcylation specifically governs the biosynthesis of tri- and tetra-antennary N-glycans via the OGT-SLC35A3-GnT-IV axis." @default.
• W4226013670 created "2022-05-05" @default.
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• W4226013670 date "2022-01-03" @default.
• W4226013670 modified "2023-10-14" @default.
• W4226013670 title "<i>O</i> ‐GlcNAcylation regulates β1,4‐GlcNAc‐branched <i>N</i> ‐glycan biosynthesis via the OGT/SLC35A3/GnT‐IV axis" @default.
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• W4226013670 doi "https://doi.org/10.1096/fj.202101520r" @default.
• W4226013670 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34981577" @default.
• W4226013670 hasPublicationYear "2022" @default.
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