Document Detail

Genome-scale identification of UDP-GlcNAc-dependent pathways.
MedLine Citation:
PMID:  18646010     Owner:  NLM     Status:  MEDLINE    
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.
Ken S Lau; Sofia Khan; James W Dennis
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proteomics     Volume:  8     ISSN:  1615-9861     ISO Abbreviation:  Proteomics     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-13     Completed Date:  2008-12-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101092707     Medline TA:  Proteomics     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  3294-302     Citation Subset:  IM    
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, ON, Canada.
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MeSH Terms
Cell Line
Cell Proliferation / drug effects
Chromatography, High Pressure Liquid
Endocytosis / drug effects
Gene Expression Profiling*
Genome, Human / genetics*
Oligonucleotide Array Sequence Analysis
RNA, Small Interfering / genetics
Signal Transduction / drug effects,  physiology*
Uridine Diphosphate N-Acetylglucosamine / metabolism*,  pharmacology
Reg. No./Substance:
0/RNA, Small Interfering; 528-04-1/Uridine Diphosphate N-Acetylglucosamine

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