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Article: Decreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient cells

TitleDecreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient cells
Authors
KeywordsPhosphatidylinositol
PKB
Glucosamine-6-phosphate acetyltransferase
Actin dynamics
Glycosylation
Issue Date2000
Citation
EMBO Journal, 2000, v. 19, n. 19, p. 5092-5104 How to Cite?
AbstractThe hexosamine pathway provides UDPN-acetylhexosamine donor substrates used in cytosolic and Golgi-mediated glycosylation of proteins and for formation of glycosylphosphatidylinositol (GPI) anchors, which tether proteins to the outer plasma membrane. We have recently identified the murine glucosamine-6-phosphate (GIcN6P) acetyltransferase, EMeg32, as a developmentally regulated enzyme on the route to UDP-N-acetylglucosamine (UDPGIcNAc). Here we describe embryos and cells that have the EMeg32 gene inactivated by homologous recombination. Homozygous mutant embryos die at around embryonic day (E) 7.5 with a general proliferative delay of development. In vitro differentiated EMeg32-(/)- ES cells show reduced proliferation. Mouse embryonic fibroblasts (MEFs) deficient for EMeg32 exhibit defects in proliferation and adhesiveness, which could be complemented by stable re-expression of EMeg32 or by nutritional restoration of intracellular UDP-GIcNAc levels. Reduced UDP-GIcNAc levels predominantly translated into decreased O-GIcNAc modifications of cytosolic and nuclear proteins. Interestingly, growth-impaired EMeg32-(/)- MEFs withstand a number of apoptotic stimuli and express activated PKB/AKT. Thus, EMeg32-dependent UDP-GIcNAc levels influence cell cycle progression and susceptibility to apoptotic stimuli.
Persistent Identifierhttp://hdl.handle.net/10722/291536
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 5.489
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBoehmelt, Guido-
dc.contributor.authorWakeham, Andrew-
dc.contributor.authorElia, Andrew-
dc.contributor.authorSasaki, Takehiko-
dc.contributor.authorPlyte, Sue-
dc.contributor.authorPotter, Julia-
dc.contributor.authorYang, Yingju-
dc.contributor.authorTsang, Eric-
dc.contributor.authorRuland, Jürgen-
dc.contributor.authorIscove, Norman N.-
dc.contributor.authorDennis, James W.-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:54:35Z-
dc.date.available2020-11-17T14:54:35Z-
dc.date.issued2000-
dc.identifier.citationEMBO Journal, 2000, v. 19, n. 19, p. 5092-5104-
dc.identifier.issn0261-4189-
dc.identifier.urihttp://hdl.handle.net/10722/291536-
dc.description.abstractThe hexosamine pathway provides UDPN-acetylhexosamine donor substrates used in cytosolic and Golgi-mediated glycosylation of proteins and for formation of glycosylphosphatidylinositol (GPI) anchors, which tether proteins to the outer plasma membrane. We have recently identified the murine glucosamine-6-phosphate (GIcN6P) acetyltransferase, EMeg32, as a developmentally regulated enzyme on the route to UDP-N-acetylglucosamine (UDPGIcNAc). Here we describe embryos and cells that have the EMeg32 gene inactivated by homologous recombination. Homozygous mutant embryos die at around embryonic day (E) 7.5 with a general proliferative delay of development. In vitro differentiated EMeg32-(/)- ES cells show reduced proliferation. Mouse embryonic fibroblasts (MEFs) deficient for EMeg32 exhibit defects in proliferation and adhesiveness, which could be complemented by stable re-expression of EMeg32 or by nutritional restoration of intracellular UDP-GIcNAc levels. Reduced UDP-GIcNAc levels predominantly translated into decreased O-GIcNAc modifications of cytosolic and nuclear proteins. Interestingly, growth-impaired EMeg32-(/)- MEFs withstand a number of apoptotic stimuli and express activated PKB/AKT. Thus, EMeg32-dependent UDP-GIcNAc levels influence cell cycle progression and susceptibility to apoptotic stimuli.-
dc.languageeng-
dc.relation.ispartofEMBO Journal-
dc.subjectPhosphatidylinositol-
dc.subjectPKB-
dc.subjectGlucosamine-6-phosphate acetyltransferase-
dc.subjectActin dynamics-
dc.subjectGlycosylation-
dc.titleDecreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient cells-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/emboj/19.19.5092-
dc.identifier.pmid11013212-
dc.identifier.pmcidPMC302091-
dc.identifier.scopuseid_2-s2.0-0034597007-
dc.identifier.volume19-
dc.identifier.issue19-
dc.identifier.spage5092-
dc.identifier.epage5104-
dc.identifier.isiWOS:000089792100006-
dc.identifier.issnl0261-4189-

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