2020
OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance
Yang Y, Li X, Luan HH, Zhang B, Zhang K, Nam JH, Li Z, Fu M, Munk A, Zhang D, Wang S, Liu Y, Albuquerque JP, Ong Q, Li R, Wang Q, Robert ME, Perry RJ, Chung D, Shulman GI, Yang X. OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 16616-16625. PMID: 32601203, PMCID: PMC7368321, DOI: 10.1073/pnas.1916121117.Peer-Reviewed Original ResearchConceptsRibosomal protein S6 kinase beta-1Macrophage proinflammatory activationGlcNAc signalingProinflammatory activationUnexpected roleWhole-body metabolismNutrient fluxesLipid accumulationImmune cell activationGlcNAcHomeostatic mechanismsMetabolic disturbancesBeta 1Cell activationDiet-induced metabolic dysfunctionDiet-induced obese miceActivationWhole-body insulin resistanceMacrophage inflammationGlcNAcylationOGTPeripheral tissuesPhosphorylationEnhanced inflammationInsulin resistanceO-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity
Yang Y, Fu M, Li MD, Zhang K, Zhang B, Wang S, Liu Y, Ni W, Ong Q, Mi J, Yang X. O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity. Nature Communications 2020, 11: 181. PMID: 31924761, PMCID: PMC6954210, DOI: 10.1038/s41467-019-13914-8.Peer-Reviewed Original ResearchMeSH KeywordsAcetylglucosamineAnimalsCell Line, TumorDietFastingGene DeletionHEK293 CellsHeLa CellsHomeostasisHumansIntra-Abdominal FatLipolysisMaleMiceMice, Inbred C3HMice, Inbred C57BLMice, KnockoutN-AcetylglucosaminyltransferasesObesityPerilipin-1PhosphorylationProtein Processing, Post-TranslationalSignal TransductionConceptsDiet-induced obesityVisceral fatExcessive visceral fat accumulationPerilipin 1Visceral fat accumulationVisceral fat lossTreatment of obesityPrimary risk factorAdipose tissue homeostasisUnhealthy obesityRisk factorsEnhanced lipolysisInhibits lipolysisFat accumulationO-GlcNAcylationFat lossObesityFat lipolysisRelated diseasesLipolysisInducible deletionLipid dropletsHexosamine biosynthetic pathwayFatTissue homeostasis
2019
O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth
Singh JP, Qian K, Lee JS, Zhou J, Han X, Zhang B, Ong Q, Ni W, Jiang M, Ruan HB, Li MD, Zhang K, Ding Z, Lee P, Singh K, Wu J, Herzog RI, Kaech S, Wendel HG, Yates JR, Han W, Sherwin RS, Nie Y, Yang X. O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth. Oncogene 2019, 39: 560-573. PMID: 31501520, PMCID: PMC7107572, DOI: 10.1038/s41388-019-0975-3.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAcetylglucosamineAnimalsAntigens, NeoplasmCarrier ProteinsCell Line, TumorDatasets as TopicDisease ProgressionFemaleGene Expression ProfilingGlycolysisHEK293 CellsHistone AcetyltransferasesHumansHyaluronoglucosaminidaseMaleMembrane ProteinsMiceN-AcetylglucosaminyltransferasesNeoplasm GradingNeoplasm StagingNeoplasmsProtein Processing, Post-TranslationalThyroid HormonesTissue Array AnalysisUp-RegulationXenograft Model Antitumor AssaysConceptsPyruvate kinase M2O-GlcNAcaseAerobic glycolysisO-GlcNAcylationKinase M2Lysine acetyltransferase activityTumor growthMetabolic rheostatAcetyltransferase activityGlcNAc transferaseMolecular basisMetabolic shiftHuman cancersGlycolysisCancer cellsHigh glucose conditionsGlucose availabilityTumor progressionGlucose conditionsExquisite controlGrowthRheostatCausative roleTargetEnzyme
2018
Adipocyte OGT governs diet-induced hyperphagia and obesity
Li MD, Vera NB, Yang Y, Zhang B, Ni W, Ziso-Qejvanaj E, Ding S, Zhang K, Yin R, Wang S, Zhou X, Fang EX, Xu T, Erion DM, Yang X. Adipocyte OGT governs diet-induced hyperphagia and obesity. Nature Communications 2018, 9: 5103. PMID: 30504766, PMCID: PMC6269424, DOI: 10.1038/s41467-018-07461-x.Peer-Reviewed Original ResearchConceptsSerine/threonine residuesN-acetylglucosamine transferaseNutrient cuesThreonine residuesTranscriptional activationO-GlcNAcylationLipid desaturationIntracellular proteinsOGTHigh-fat diet-induced hyperphagiaDevelopment of obesityBaseline food intakeSignaling contributesLipid signalsCB1 signalingBrain axisChronic dysregulationFood intakeMetabolic diseasesPalatable foodPharmacological manipulationHyperphagiaObesityFat sensorSignaling
2017
Protein O-GlcNAcylation: emerging mechanisms and functions
Yang X, Qian K. Protein O-GlcNAcylation: emerging mechanisms and functions. Nature Reviews Molecular Cell Biology 2017, 18: 452-465. PMID: 28488703, PMCID: PMC5667541, DOI: 10.1038/nrm.2017.22.Peer-Reviewed Original ResearchMeSH KeywordsAcetylglucosamineAnimalsHumansN-AcetylglucosaminyltransferasesProtein Processing, Post-TranslationalProteinsSignal TransductionConceptsPost-translational modificationsO-GlcNAcylationAdaptor proteinGlcNAcylation levelsO-GlcNAc homeostasisTetratricopeptide repeat domainDiverse cellular processesProtein-protein interactionsOptimal cellular functionContext-dependent recruitmentPost-translational levelCell signaling dynamicsUnwanted protein aggregationCellular O-GlcNAcylationSubstrate-specific interactionsSpecific cell typesN-acetylglucosamine moietiesLevels of OGTGlcNAc signalingMitochondrial proteinsSpatiotemporal regulationCellular functionsCellular processesEpigenetic modificationsProtein substrates
2013
O-GlcNAc Signaling Entrains the Circadian Clock by Inhibiting BMAL1/CLOCK Ubiquitination
Li MD, Ruan HB, Hughes ME, Lee JS, Singh JP, Jones SP, Nitabach MN, Yang X. O-GlcNAc Signaling Entrains the Circadian Clock by Inhibiting BMAL1/CLOCK Ubiquitination. Cell Metabolism 2013, 17: 303-310. PMID: 23395176, PMCID: PMC3647362, DOI: 10.1016/j.cmet.2012.12.015.Peer-Reviewed Original ResearchConceptsCircadian clockProtein modificationNutrient-sensing pathwaysO-GlcNAc signalingHexosamine biosynthesis pathwayCovalent protein modificationBiosynthesis pathwayGlcNAc transferaseNutritional signalsClock oscillationsO-GlcNAcylationAberrant circadian rhythmsClock targetsOGT expressionCircadian oscillationsUbiquitinationN-acetylglucosamineNutrient fluxesMetabolic oscillationsBMAL1GenesPathwayCircadian rhythmKey mechanismClock
2008
Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance
Yang X, Ongusaha PP, Miles PD, Havstad JC, Zhang F, So WV, Kudlow JE, Michell RH, Olefsky JM, Field SJ, Evans RM. Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance. Nature 2008, 451: 964-969. PMID: 18288188, DOI: 10.1038/nature06668.Peer-Reviewed Original ResearchMeSH KeywordsAcetylglucosamineAnimalsCell MembraneChlorocebus aethiopsCOS CellsInsulinInsulin ResistanceLipid MetabolismLiverMaleMiceMice, Inbred C57BLN-AcetylglucosaminyltransferasesPhosphatidylinositol PhosphatesPhosphatidylinositolsPhosphorylationProtein Structure, TertiaryProtein TransportSecond Messenger SystemsConceptsO-GlcNAcSignal transductionPhosphoinositide-binding domainsPost-translational modificationsO-GlcNAc transferaseHexosamine biosynthetic pathwayInsulin signal transductionInsulin-responsive genesCellular regulationGlcNAc transferaseNutritional cuesNuclear proteinsBiosynthetic pathwayPlasma membraneProtein degradationNutrient sensorMolecular mechanismsN-acetylglucosamineTransductionPathwayTransferaseHepatic overexpressionGlucose fluxDynamic modificationMetabolic status