2025
Decoding Extracellular Protein Glycosylation in Human Health and Disease.
Steigmeyer A, Lowery S, Rangel-Angarita V, Malaker S. Decoding Extracellular Protein Glycosylation in Human Health and Disease. Annual Review Of Analytical Chemistry 2025 PMID: 39813736, DOI: 10.1146/annurev-anchem-071024-124203.Peer-Reviewed Original ResearchPost-translational modificationsProtein glycosylationStudy protein glycosylationHeterogeneous post-translational modificationsBiologically relevant contextProtein foldingGlycan complexityNontemplated natureCell adhesionAberrant glycosylationProtein backboneGlycosylationBiochemical processesProteinGlycoprotein characterizationCovalent attachmentHealth and DiseaseGlycansStructural heterogeneityHuman healthRelevant contextGlycoproteinFoldingBiologyN-
2024
Development of a High-Throughput Platform for Quantitation of Histone Modifications on a New QTOF Instrument
Zahn E, Xie Y, Liu X, Karki R, Searfoss R, de Luna Vitorino F, Lempiäinen J, Gongora J, Lin Z, Zhao C, Yuan Z, Garcia B. Development of a High-Throughput Platform for Quantitation of Histone Modifications on a New QTOF Instrument. Molecular & Cellular Proteomics 2024, 24: 100897. PMID: 39708910, PMCID: PMC11787651, DOI: 10.1016/j.mcpro.2024.100897.Peer-Reviewed Original ResearchConceptsData-independent acquisitionModified histone peptidesLC-MSMass spectrometry (MS)-based approachesMicroflow liquid chromatographyNanoflow LC-MSPost-translational modificationsIsobaric peptidesQTOF instrumentLC gradientSequential window acquisitionHistone post-translational modificationsMass spectrometerHistone peptidesTransforming growth factor beta 1Histone deacetylase inhibitorsHistone samplesWindow acquisitionOrbitrapLow stoichiometryLiquid chromatographyCharacterization of histone PTMsHigh-throughput methodDeacetylase inhibitorsInstrumentation timeSpatiotemporal control of subcellular O-GlcNAc signaling using Opto-OGT
Ong Q, Lim L, Goh C, Liao Y, Chan S, Lim C, Kam V, Yap J, Tseng T, Desrouleaux R, Wang L, Ler S, Lim S, Kim S, Sobota R, Bennett A, Han W, Yang X. Spatiotemporal control of subcellular O-GlcNAc signaling using Opto-OGT. Nature Chemical Biology 2024, 21: 300-308. PMID: 39543398, DOI: 10.1038/s41589-024-01770-7.Peer-Reviewed Original ResearchO-GlcNAc transferaseO-GlcNAcLocalized to specific subcellular sitesResponse to insulin stimulationPost-translational modification of intracellular proteinsModification of intracellular proteinsO-GlcNAc signalingPost-translational modificationsTargeting O-GlcNAc transferaseSpatiotemporal controlMulticellular organismsOGT activityOrganelle functionO-GlcNAcylationSubcellular sitesMTORC activitySignal transductionIntracellular proteinsNutrient-sensing signalsCell signalingInsulin stimulationPlasma membraneGene expressionRegulatory mechanismsAkt phosphorylationQuantification and Site-Specific Analysis of Co-occupied N- and O‑Glycopeptides
Chongsaritsinsuk J, Rangel-Angarita V, Lucas T, Mahoney K, Enny O, Katemauswa M, Malaker S. Quantification and Site-Specific Analysis of Co-occupied N- and O‑Glycopeptides. Journal Of Proteome Research 2024, 23: 5449-5461. PMID: 39498894, DOI: 10.1021/acs.jproteome.4c00574.Peer-Reviewed Original ResearchElectron-based methodsO-glycopeptidesElectron-based fragmentation methodsFragmentation methodCo-occupancyO-glycosylated peptidesAnalysis of glycopeptidesPost-translational modificationsN-glycoproteomic analysisCore 1 structureComplex samplesO-glycansPurified proteinProtein glycosylationO-glycositesN-glycoproteomeNonmucin glycoproteinsTryptic peptidesDissociation methodO-linkedAnalysis of mucinsSite-specific analysisGlycoproteinGlycosylationProteinUnraveling the Drivers of the Stress Granule Signature in Splicing Factor-Mutant Myeloid Malignancies
Biancon G, Busarello E, Cheng M, Sidoli S, VanOudenhove J, Bucciarelli G, Tebaldi T, Halene S. Unraveling the Drivers of the Stress Granule Signature in Splicing Factor-Mutant Myeloid Malignancies. Blood 2024, 144: 4117. DOI: 10.1182/blood-2024-211265.Peer-Reviewed Original ResearchRNA-binding proteinsStress granulesRNA-seqArsenite stressSF mutationsAcute myeloid leukemiaSplicing factorsSG proteinsStress responseClonal advantageSG coresMulti-omicsDeregulated genesMyelodysplastic syndromeEnhances SG formationU2AF1 S34F mutationSingle-cell RNA-seqWT cellsMegakaryocyte-erythroid progenitorsRegulation of translationTranslation initiation factorsImprove cell fitnessRNA-seq analysisPost-translational modificationsU2AF1 mutationsDiscovery and clinical translation of ceperognastat, an O‐GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease
Kielbasa W, Goldsmith P, Donnelly K, Nuthall H, Shcherbinin S, Fleisher A, Hendle J, DuBois S, Lowe S, Zhang F, Woerly E, Dreyfus N, Evans D, Gilmore J, Mancini M, Constantinescu C, Gunn R, Russell D, Collins E, Brys M, Hutton M, Mergott D. Discovery and clinical translation of ceperognastat, an O‐GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2024, 10: e70020. PMID: 39748851, PMCID: PMC11694536, DOI: 10.1002/trc2.70020.Peer-Reviewed Original ResearchReduced tau pathologyO-GlcNAcaseOGA inhibitorsO-GlcNAcO-GlcNAcylationPost-translational modifications of tauTau pathologyAlzheimer's diseaseTau O-GlcNAcylationRemoval of O-GlcNAcModifications of tauO-GlcNAcase inhibitionPost-translational modificationsInhibitor of O-GlcNAcaseO-GlcNAcase inhibitorProgression of ADEnzyme occupancyTauopathy modelPathological tauPhase 1 clinical studyTreatment of Alzheimer's diseaseHuman brainEnzyme activityPatients relative to healthy controlsPotential therapeutic approachBeyond glucose: The crucial role of redox signaling in β-cell metabolic adaptation
Holendová B, Šalovská B, Benáková Š, Plecitá-Hlavatá L. Beyond glucose: The crucial role of redox signaling in β-cell metabolic adaptation. Metabolism 2024, 161: 156027. PMID: 39260557, DOI: 10.1016/j.metabol.2024.156027.Peer-Reviewed Original ResearchPost-translational modificationsReactive oxygen speciesEndoplasmic reticulumTricarboxylic acidRedox signalingPancreatic B-cellsGlucose stimulationModification of proteinsB-cell metabolismRedox signaling pathwaysReversible cysteine oxidationIncreased ROS levelsProduction of reactive oxygen speciesB cell functionInsulin secretionB cellsProtein functionProtein processingCysteine thiol modificationsGlucose-induced increaseOxidative phosphorylationPyruvate metabolismProtein activityRegulatory mechanismsMetabolic pathwaysOrganization of a functional glycolytic metabolon on mitochondria for metabolic efficiency
Wang H, Vant J, Zhang A, Sanchez R, Wu Y, Micou M, Luczak V, Whiddon Z, Carlson N, Yu S, Jabbo M, Yoon S, Abushawish A, Ghassemian M, Masubuchi T, Gan Q, Watanabe S, Griffis E, Hammarlund M, Singharoy A, Pekkurnaz G. Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency. Nature Metabolism 2024, 6: 1712-1735. PMID: 39261628, DOI: 10.1038/s42255-024-01121-9.Peer-Reviewed Original ResearchConceptsO-GlcNAc transferaseO-GlcNAcylation sitesGlycolytic metabolonO-GlcNAcylationEnzyme O-GlcNAc transferaseOuter mitochondrial membraneDynamic O-GlcNAcylationPost-translational modificationsReduced ATP generationMitochondrial ATP productionMetabolic efficiencyEnergy-demanding tissuesCellular energy sourceOGT activityMitochondrial associationRegulatory domainMitochondrial membraneMultiple cell typesATP generationATP productionMitochondrial functionMitochondrial couplingMetabolonCell typesGlucose fluxGlycoproteomics: Charting new territory in mass spectrometry and glycobiology
Malaker S. Glycoproteomics: Charting new territory in mass spectrometry and glycobiology. Journal Of Mass Spectrometry 2024, 59: e5034. PMID: 38726698, DOI: 10.1002/jms.5034.Peer-Reviewed Original ResearchProtein oxidation of fucose environments (POFE) reveals fucose–protein interactions
Xie Y, Chen S, Alvarez M, Sheng Y, Li Q, Maverakis E, Lebrilla C. Protein oxidation of fucose environments (POFE) reveals fucose–protein interactions. Chemical Science 2024, 15: 5256-5267. PMID: 38577366, PMCID: PMC10988611, DOI: 10.1039/d3sc06432h.Peer-Reviewed Original ResearchProtein-protein interactionsCopper-catalyzed click chemistryFormation of hydroxyl radicalsCell membrane glycoproteinMembrane glycoproteinPost-translational modificationsLiquid chromatography coupled with tandem mass spectrometryTandem mass spectrometryClick chemistryBinding partnersGalectin-3-binding proteinProtein functionCellular processesMammalian cellsMass spectrometryOxidized peptidesFucose residuesHydroxyl radicalsLabeled probesBioorthogonal groupsLC-MS/MSAmino acidsProteinFucoseProtein oxidation
2023
Acetyl-methyllysine marks chromatin at active transcription start sites
Lu-Culligan W, Connor L, Xie Y, Ekundayo B, Rose B, Machyna M, Pintado-Urbanc A, Zimmer J, Vock I, Bhanu N, King M, Garcia B, Bleichert F, Simon M. Acetyl-methyllysine marks chromatin at active transcription start sites. Nature 2023, 622: 173-179. PMID: 37731000, PMCID: PMC10845139, DOI: 10.1038/s41586-023-06565-9.Peer-Reviewed Original ResearchConceptsPost-translational modificationsLysine residuesActive transcription start sitesTranscription start siteRange of speciesChromatin biologyChromatin proteinsLysine methylationActive chromatinProteins BRD2Transcriptional initiationLysine acetylationHistone H4Start siteMammalian tissuesHuman diseasesSame residuesMethylationAcetylationChromatinResiduesProteinBiological signalsHistonesBRD2Scalable production of tissue-like vascularized liver organoids from human PSCs
Harrison S, Siller R, Tanaka Y, Chollet M, de la Morena-Barrio M, Xiang Y, Patterson B, Andersen E, Bravo-Pérez C, Kempf H, Åsrud K, Lunov O, Dejneka A, Mowinckel M, Stavik B, Sandset P, Melum E, Baumgarten S, Bonanini F, Kurek D, Mathapati S, Almaas R, Sharma K, Wilson S, Skottvoll F, Boger I, Bogen I, Nyman T, Wu J, Bezrouk A, Cizkova D, Corral J, Mokry J, Zweigerdt R, Park I, Sullivan G. Scalable production of tissue-like vascularized liver organoids from human PSCs. Experimental & Molecular Medicine 2023, 55: 2005-2024. PMID: 37653039, PMCID: PMC10545717, DOI: 10.1038/s12276-023-01074-1.Peer-Reviewed Original ResearchConceptsExtracellular matrixSingle-cell RNA sequencingBasic developmental biologyEmbryonic liver developmentPost-translational modificationsLiver-like functionsCostly growth factorsOrganoid modelsKey liver functionsCellular diversityCellular repertoireDevelopmental biologyCellular complexityN-glycosylationRNA sequencingDe novo vascularizationNumber of tissuesProtein productionSerum protein productionLiver developmentHuman PSCsDrug toxicity assessmentOrganoidsSmall moleculesGrowth factorSystem‐wide optimization of an orthogonal translation system with enhanced biological tolerance
Mohler K, Moen J, Rogulina S, Rinehart J. System‐wide optimization of an orthogonal translation system with enhanced biological tolerance. Molecular Systems Biology 2023, 19: msb202110591. PMID: 37477096, PMCID: PMC10407733, DOI: 10.15252/msb.202110591.Peer-Reviewed Original ResearchConceptsOrthogonal translation systemHost interactionsNon-standard amino acidsPost-translational modificationsSystems-level biologyStress response activationTranslation systemSynthetic biological systemsCellular physiologyProtein phosphorylationOTS performanceHost physiologyCellular environmentAmino acidsCellular mechanismsDeleterious interactionsResponse activationBiological systemsPhysiologyOTS developmentUnparalleled accessPhosphorylationHost toxicityBiologyInteractionPyroptosis in cardiovascular diseases: Pumping gasdermin on the fire
Yarovinsky T, Su M, Chen C, Xiang Y, Tang W, Hwa J. Pyroptosis in cardiovascular diseases: Pumping gasdermin on the fire. Seminars In Immunology 2023, 69: 101809. PMID: 37478801, PMCID: PMC10528349, DOI: 10.1016/j.smim.2023.101809.Peer-Reviewed Original ResearchConceptsPost-translational modificationsAcute cardiovascular eventsChronic cardiovascular diseaseCardiovascular diseaseSmall molecule inhibitorsPyroptosis resultsGenetic toolsGasdermin proteinsWhole organismInflammatory caspasesCardiovascular eventsCell deathMolecule inhibitorsCell typesProteolytic cleavageCellular mechanismsActivation of inflammasomesCardiovascular systemKnockout animalsAmplification of inflammationRole of pyroptosisPro-inflammatory processesDifferent cellsNovel therapeutic approachesPyroptosisAcetylation of MLH1 by CBP increases cellular DNA mismatch repair activity
Zhang M, Zhao J, Glazer P, Bai W, Bepler G, Zhang X. Acetylation of MLH1 by CBP increases cellular DNA mismatch repair activity. The Journal Of Biochemistry 2023, 174: 183-191. PMID: 37094360, DOI: 10.1093/jb/mvad034.Peer-Reviewed Original ResearchConceptsMutLα complexMMR activityUbiquitin-proteasome degradation pathwayDNA mismatch repair activityDNA damage responsePost-translational modificationsCell cycle checkpointsOverexpression of CBPMismatch repair activityDNA base pair mismatchesInsertions/deletionsDNA mismatch repair proteinsGenomic integrityDamage responseDNA replicationCycle checkpointsRepair proteinsTrichostatin ABase pair mismatchesNovel roleMismatch repair proteinsRepair activityCBPProteinDeacetylase inhibitorsUncovering biology by single-cell proteomics
Mansuri M, Williams K, Nairn A. Uncovering biology by single-cell proteomics. Communications Biology 2023, 6: 381. PMID: 37031277, PMCID: PMC10082756, DOI: 10.1038/s42003-023-04635-2.Peer-Reviewed Original ResearchActivity‐based Tools for Interrogating Host Biology During Infection
Ramanathan R, Hatzios S. Activity‐based Tools for Interrogating Host Biology During Infection. Israel Journal Of Chemistry 2023, 63 PMID: 37744997, PMCID: PMC10512441, DOI: 10.1002/ijch.202200095.Peer-Reviewed Original ResearchActivity-based protein profilingPost-translational modificationsHost post-translational modificationsHost-microbe interactionsHost biologyCells senseCell signalingMicrobial mechanismsEnzyme functionProtein profilingProtein structureSide-chain reactivityChemical probesInfected cellsHost-directed therapiesPotential targetRapid modulationHost responseSignalingBiologyInfectionEnzymeProfilingPathwayPathogensDual incorporation of non-canonical amino acids enables production of post-translationally modified selenoproteins
Morosky P, Comyns C, Nunes L, Chung C, Hoffmann P, Söll D, Vargas-Rodriguez O, Krahn N. Dual incorporation of non-canonical amino acids enables production of post-translationally modified selenoproteins. Frontiers In Molecular Biosciences 2023, 10: 1096261. PMID: 36762212, PMCID: PMC9902344, DOI: 10.3389/fmolb.2023.1096261.Peer-Reviewed Original ResearchPost-translational modificationsGenetic code expansionAmino acidsProtein functionCode expansionNon-canonical amino acidsGenetic code expansion techniqueOrthogonal translation systemSkeletal muscle regenerationSelenoprotein functionCell maintenanceBiosynthesis mechanismGenetic systemSelenocysteine insertionPreferred hostMultiple proteinsBiological processesBiology applicationsProtein positionsStop codonCodon sequenceProtein sitesSelenoproteinsChemical biology applicationsMuscle regenerationAn atlas of substrate specificities for the human serine/threonine kinome
Johnson J, Yaron T, Huntsman E, Kerelsky A, Song J, Regev A, Lin T, Liberatore K, Cizin D, Cohen B, Vasan N, Ma Y, Krismer K, Robles J, van de Kooij B, van Vlimmeren A, Andrée-Busch N, Käufer N, Dorovkov M, Ryazanov A, Takagi Y, Kastenhuber E, Goncalves M, Hopkins B, Elemento O, Taatjes D, Maucuer A, Yamashita A, Degterev A, Uduman M, Lu J, Landry S, Zhang B, Cossentino I, Linding R, Blenis J, Hornbeck P, Turk B, Yaffe M, Cantley L. An atlas of substrate specificities for the human serine/threonine kinome. Nature 2023, 613: 759-766. PMID: 36631611, PMCID: PMC9876800, DOI: 10.1038/s41586-022-05575-3.Peer-Reviewed Original ResearchConceptsSer/ThrHuman Ser/ThrSubstrate specificityPhosphorylation eventsProtein serine/threonine kinaseWidespread post-translational modificationSerine/threonine kinasePutative protein kinaseSubstrate sequence specificityIntrinsic substrate specificityPost-translational modificationsThreonine phosphorylationGenetic perturbationsThreonine kinasePhosphorylation sitesHuman genomeProtein phosphorylationProtein kinaseSequence specificityBiological pathwaysHuman diseasesNegative selectivityKinaseUnexpected insightsKinome3108 – PHOSPHORYLATION OF RUNX1 PROMOTES MEGAKARYOCYTIC FATE IN MEGAKARYOCYTE-ERYTHROID PROGENITOR FATE SPECIFICATION
Kwon N, Lu Y, Thompson E, Wang L, Zhang P, Krause D. 3108 – PHOSPHORYLATION OF RUNX1 PROMOTES MEGAKARYOCYTIC FATE IN MEGAKARYOCYTE-ERYTHROID PROGENITOR FATE SPECIFICATION. Experimental Hematology 2023, 124: s104. DOI: 10.1016/j.exphem.2023.06.215.Peer-Reviewed Original ResearchMegakaryocyte-erythroid progenitorsFate specificationHEL cellsGene expressionSingle-cell RNA-seq dataPost-translational modificationsDifferential gene expressionRNA-seq dataChromatin localizationRNA-seqPhosphorylation statusRUNX1 overexpressionE progenitorsTranscriptional activityKey regulatorRUNX1 mRNAMK progenitorsT residuesGenesErythroid progenitorsRUNX1MKPProgenitorsProtein levelsSpecification mechanism
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