Genome-scale identification of UDP-GlcNAc-dependent pathways.

Lau KS, Khan S, Dennis JW
Proteomics. 2008 8 (16): 3294-302

PMID: 18646010 · DOI:10.1002/pmic.200800208

Metabolite flux to UDP-GlcNAc and Golgi N-glycan biosynthesis regulates surface residency of glycoprotein receptors and transporters, and thus sensitivities of cells to extracellular cues. Salvage of GlcNAc increases UDP-GlcNAc and branching of N-glycans progressively, but displays an optimum for cell proliferation and bulk endocytosis in mouse NMuMG and human HEK293T epithelial cells. In this report, we measured global changes in gene expression in low and high GlcNAc-supplemented cells. Genes upregulated by high GlcNAc included the EGF and TGF-beta signaling pathways and cell cycle checkpoint, while downregulated genes indicated lower metabolic activity. Genes increased or decreased by high GlcNAc were assessed by transfecting cells with small interfering RNA (siRNA) and measuring effects on three phenotypes: proliferation and bulk endocytosis, and beta1,6GlcNAc-branching of N-glycans. siRNA targeting LGALS3, WBSCR17, PHF3, SDC2 and CTNNAL1 partially reversed the GlcNAc-induced phenotypes, suggesting a role for galectin-3/N-glycans, proteoglycans, O-glycans, and junctional cell adhesion.

MeSH Terms (12)

Animals Cell Line Cell Proliferation Chromatography, High Pressure Liquid Endocytosis Gene Expression Profiling Genome, Human Humans Oligonucleotide Array Sequence Analysis RNA, Small Interfering Signal Transduction Uridine Diphosphate N-Acetylglucosamine

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