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Deng Z. A relatively low glucose promotes the proliferation of vascular endothelial cells by suppressing VEGFR2 O-GlcNAcylation and its proteasome degradation. International ophthalmology 2023 43(3) 36089631
Vascular endothelial growth factor receptors (VEGFRs) have been demonstrated to play a critical role in ischemic retinal diseases, as VEGFRs mediate hypoxia-induced neovascularization. Not only hypoxia, ischemia also induces the deficiency of glucose, yet its effects on VEGFR signal and neovascularization have seldom been studied. Bioinformatics analysis predicted that VEGFRs may be regulated by O-GlcNAcylation, while glucose deficiency influences the O-GlcNAcylation.
O-GlcNAc proteins:
Species: Homo sapiens
Liu J, Hao Y, Wang C, Jin Y, Yang Y, Gu J, Chen X. An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. ACS chemical biology 2022 17(3) 35254053
O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. Of the thousands of O-GlcNAcylated proteins identified, many carry multiple modification sites with varied stoichiometry. To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. In HeLa cells, ∼1500 O-GlcNAcylation sites were identified with the optimized procedures, which led to quantification of ∼1000 O-GlcNAcylation sites with isoPTOP. Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. The stoichiometric differences of 625 O-GlcNAcylation sites are quantified. Of these quantified sites, many occur on important regulators involved in tumor progression and metastasis. Our results provide a valuable database for understanding the functional role of O-GlcNAc in CRC. IsoPTOP should be applicable for investigating O-GlcNAcylation dynamics in various pathophysiological processes.