2024
PTMoreR-enabled cross-species PTM mapping and comparative phosphoproteomics across mammals
Wang S, Di Y, Yang Y, Salovska B, Li W, Hu L, Yin J, Shao W, Zhou D, Cheng J, Liu D, Yang H, Liu Y. PTMoreR-enabled cross-species PTM mapping and comparative phosphoproteomics across mammals. Cell Reports Methods 2024, 4: 100859. PMID: 39255793, PMCID: PMC11440062, DOI: 10.1016/j.crmeth.2024.100859.Peer-Reviewed Original ResearchConceptsP-siteSurrounding amino acid sequenceKinase-substrate networkQuantitative phosphoproteomic analysisFunctional enrichment analysisPhosphoproteomic resultsKinase motifsComparative phosphoproteomicsPTM sitesPhosphorylation eventsPhosphoproteomic analysisProteomic analysisEnrichment analysisMammalian speciesSpeciesEvolutionary anglePhosphoproteomeMotifEnvironmental factorsNon-human speciesPTMProteomicsKinaseMammalsProtein
2023
Oncogene-like addiction to aneuploidy in human cancers
Girish V, Lakhani A, Thompson S, Scaduto C, Brown L, Hagenson R, Sausville E, Mendelson B, Kandikuppa P, Lukow D, Yuan M, Stevens E, Lee S, Schukken K, Akalu S, Vasudevan A, Zou C, Salovska B, Li W, Smith J, Taylor A, Martienssen R, Liu Y, Sun R, Sheltzer J. Oncogene-like addiction to aneuploidy in human cancers. Science 2023, 381: eadg4521. PMID: 37410869, PMCID: PMC10753973, DOI: 10.1126/science.adg4521.Peer-Reviewed Original ResearchAn optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells
Zhou W, Li W, Wang S, Salovska B, Hu Z, Tao B, Di Y, Punyamurtula U, Turk B, Sessa W, Liu Y. An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells. Nature Communications 2023, 14: 3803. PMID: 37365174, PMCID: PMC10293293, DOI: 10.1038/s41467-023-39514-1.Peer-Reviewed Original ResearchConceptsPhosphorylation sitesSerine/threonine kinase AktMass spectrometry-based phosphoproteomicsThreonine kinase AktAkt-dependent phosphorylationAberrant Akt activationEndothelial cellsKinase substrateKinase AktCell signalingPhosphorylation profilePhenotypic outcomesDownstream signalingAkt activationAkt1 phosphorylationHuman diseasesSystem-level analysisAKT1Vascular endothelial cellsRich resourcePhosphorylationSignalingGrowth factorAktCellsPhosphoproteomic analysis of metformin signaling in colorectal cancer cells elucidates mechanism of action and potential therapeutic opportunities
Salovska B, Gao E, Müller‐Dott S, Li W, Cordon C, Wang S, Dugourd A, Rosenberger G, Saez‐Rodriguez J, Liu Y. Phosphoproteomic analysis of metformin signaling in colorectal cancer cells elucidates mechanism of action and potential therapeutic opportunities. Clinical And Translational Medicine 2023, 13: e1179. PMID: 36781298, PMCID: PMC9925373, DOI: 10.1002/ctm2.1179.Peer-Reviewed Original ResearchConceptsColorectal cancerLong-term metformin treatmentType 2 diabetesCRC cell linesColorectal cancer cellsBiguanide drug metforminPotential therapeutic opportunitiesMechanism of actionPharmacodynamic interactionsMetformin treatmentTreatment of cancerCRC cellsCell proliferation assaysClinical trialsBcl-2/Bcl-xL inhibitorMetforminDrug metforminTherapeutic opportunitiesProliferation assaysCancer cellsPotential cancer therapeuticsPotential roleExpression levelsCell linesCancer therapeutics
2021
Limited Proteolysis-Coupled Mass Spectrometry Identifies Phosphatidylinositol 4,5-Bisphosphate Effectors in Human Nuclear Proteome
Sztacho M, Šalovská B, Červenka J, Balaban C, Hoboth P, Hozák P. Limited Proteolysis-Coupled Mass Spectrometry Identifies Phosphatidylinositol 4,5-Bisphosphate Effectors in Human Nuclear Proteome. Cells 2021, 10: 68. PMID: 33406800, PMCID: PMC7824793, DOI: 10.3390/cells10010068.Peer-Reviewed Original ResearchConceptsGene expressionHuman nuclear proteomeLimited proteolysisLabel-free quantitative mass spectrometryNuclear pore complexGene ontology analysisCell cycle regulationQuantitative mass spectrometryNuclear proteomeProtein effectorsPore complexPol IIRNA splicingOntology analysisMRNA splicingCycle regulationPIP2 bindingProtein interactionsDNA repairBioinformatics analysisNuclear envelopeFunctional domainsMass spectrometry identifiesSpecific proteinsCell cycle
2020
Exosomes released by imatinib-resistant K562 cells contain specific membrane markers, IFITM3, CD146 and CD36 and increase the survival of imatinib-sensitive cells in the presence of imatinib
Hrdinova T, Toman O, Dresler J, Klimentova J, Salovska B, Pajer P, Bartos O, Polivkova V, Linhartova J, Machova Polakova K, Kabickova H, Brodska B, Krijt M, Zivny J, Vyoral D, Petrak J, Hrdinova T, Toman O, Dresler J, Klimentova J, Salovska B, Pajer P, Bartos O, Polivkova V, Linhartova J, Machova Polakova K, Kabickova H, Brodska B, Krijt M, Zivny J, Vyoral D, Petrak J. Exosomes released by imatinib-resistant K562 cells contain specific membrane markers, IFITM3, CD146 and CD36 and increase the survival of imatinib-sensitive cells in the presence of imatinib. International Journal Of Oncology 2020, 58: 238-250. PMID: 33491750, DOI: 10.3892/ijo.2020.5163.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsChronic myeloid leukemiaImatinib-resistant K562 cellsCML therapyImatinib-sensitive K562 cellsDrug resistanceK562 cellsTargeted CML therapySubset of patientsLess common mutationsSpecific tyrosine kinase inhibitorTKI drug resistanceInterferon-induced transmembrane protein 3Presence of imatinibQuality of lifeMalignant hematopoietic disordersPotential diagnostic markerFlow cytometric analysisBCR-ABL1 geneConstitutive kinase activityCell surface markersLabel-free quantification proteomics analysisMutation-independent mechanismTransmembrane protein 3Development of resistanceGlobal and Site-Specific Effect of Phosphorylation on Protein Turnover
Wu C, Ba Q, Lu D, Li W, Salovska B, Hou P, Mueller T, Rosenberger G, Gao E, Di Y, Zhou H, Fornasiero EF, Liu Y. Global and Site-Specific Effect of Phosphorylation on Protein Turnover. Developmental Cell 2020, 56: 111-124.e6. PMID: 33238149, PMCID: PMC7855865, DOI: 10.1016/j.devcel.2020.10.025.Peer-Reviewed Original ResearchConceptsProtein turnoverProtein lifetimeCyclin-dependent kinase substrateStable isotope-labeled amino acidsSite-specific phosphorylationPulse-labeling approachIsotope-labeled amino acidsMass spectrometry-based methodCell fitnessKinase substratePhosphorylation sitesPhosphorylated sitesProteomic methodsCell signalingSpectrometry-based methodsLive cellsAmino acidsPhosphositesRich resourceDisease biologyLabeling approachPhosphorylationModification typesGlutamic acidTurnoverAberrantly elevated suprabasin in the bone marrow as a candidate biomarker of advanced disease state in myelodysplastic syndromes
Pribyl M, Hubackova S, Moudra A, Vancurova M, Polackova H, Stopka T, Jonasova A, Bokorova R, Fuchs O, Stritesky J, Salovska B, Bartek J, Hodny Z. Aberrantly elevated suprabasin in the bone marrow as a candidate biomarker of advanced disease state in myelodysplastic syndromes. Molecular Oncology 2020, 14: 2403-2419. PMID: 32696549, PMCID: PMC7530796, DOI: 10.1002/1878-0261.12768.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, DifferentiationAzacitidineBiomarkersBone MarrowCell CompartmentationCell Line, TumorChemokine CCL2Gene Expression Regulation, NeoplasticHEK293 CellsHumansInterferon-gammaLeukocytes, MononuclearLymphocyte CountMyelodysplastic SyndromesMyeloid CellsNeoplasm ProteinsPrognosisProto-Oncogene MasRNA, MessengerConceptsMyelodysplastic syndromeBone marrowMDS patientsPoor prognosisDisease progressionCandidate biomarkersHigh-risk myelodysplastic syndromeMyeloid-derived suppressor cellsAberrant cytokine levelsAdvanced disease stateMyeloid cell subpopulationsBlast percentageChemokine levelsCytokine levelsLymphocyte countSuppressor cellsPatient groupPeripheral bloodBM plasmaPreleukemic disordersImmune responseProinflammatory signalingMalignant cloneTherapy resistanceLeukemic cellsIsoform‐resolved correlation analysis between mRNA abundance regulation and protein level degradation
Salovska B, Zhu H, Gandhi T, Frank M, Li W, Rosenberger G, Wu C, Germain P, Zhou H, Hodny Z, Reiter L, Liu Y. Isoform‐resolved correlation analysis between mRNA abundance regulation and protein level degradation. Molecular Systems Biology 2020, 16: msb199170. PMID: 32175694, PMCID: PMC7073818, DOI: 10.15252/msb.20199170.Peer-Reviewed Original ResearchConceptsProtein degradationGenome-wide correlation analysisGene dosage variationProtein abundance levelsStable isotope-labeled amino acidsIndividual protein isoformsSpecific biological processesAlternative splicing isoformsData-independent acquisition mass spectrometryIsotope-labeled amino acidsAcquisition mass spectrometryProtein degradation ratesIntron retentionCellular functionsProtein isoformsSplicing isoformsCellular organellesTranscriptome variabilitySame geneTurnover controlRegulatory mechanismsBiological processesSpecific mRNAsTight associationAbundance levels
2019
Combining Rapid Data Independent Acquisition and CRISPR Gene Deletion for Studying Potential Protein Functions: A Case of HMGN1
Mehnert M, Li W, Wu C, Salovska B, Liu Y. Combining Rapid Data Independent Acquisition and CRISPR Gene Deletion for Studying Potential Protein Functions: A Case of HMGN1. Proteomics 2019, 19: e1800438. PMID: 30901150, DOI: 10.1002/pmic.201800438.Peer-Reviewed Original ResearchConceptsChromosomal protein HMG-14DIA-MSDIA mass spectrometryPotential protein functionsCRISPR-Cas gene editingImmune regulation processesCancer cellsExtracellular proteomeChromatin structureHistone inactivationFunctional annotationProtein functionCellular functionsRegulation eventsImportant functional implicationsHMG 14Gene knockoutEnrichment analysisData-independent acquisitionHMGN1Protein deletionCRISPR experimentsGene editingStress pathwaysIndependent acquisitionInterferon‐regulated suprabasin is essential for stress‐induced stem‐like cell conversion and therapy resistance of human malignancies
Hubackova S, Pribyl M, Kyjacova L, Moudra A, Dzijak R, Salovska B, Strnad H, Tambor V, Imrichova T, Svec J, Vodicka P, Vaclavikova R, Rob L, Bartek J, Hodny Z. Interferon‐regulated suprabasin is essential for stress‐induced stem‐like cell conversion and therapy resistance of human malignancies. Molecular Oncology 2019, 13: 1467-1489. PMID: 30919591, PMCID: PMC6599850, DOI: 10.1002/1878-0261.12480.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinase/ERK kinaseSiRNA-mediated knockdownSBSN expressionERK pathwayProtein kinase/ERK kinaseHundreds of genesExtracellular signal-regulated kinase 1/2Signal-regulated kinase 1/2MEK/ERK pathwayCancer cellsPhenotypic plasticityTranscript profilesStress resistanceTherapy resistanceERK kinaseStem-like cellsActive NotchStem cell markersMolecular mechanismsAnoikis resistanceKinase 1/2Cancer evolutionChemical inhibitionCancer cell linesHuman clinical specimensAssessing the Relationship Between Mass Window Width and Retention Time Scheduling on Protein Coverage for Data-Independent Acquisition
Li W, Chi H, Salovska B, Wu C, Sun L, Rosenberger G, Liu Y. Assessing the Relationship Between Mass Window Width and Retention Time Scheduling on Protein Coverage for Data-Independent Acquisition. Journal Of The American Society For Mass Spectrometry 2019, 30: 1396-1405. PMID: 31147889, DOI: 10.1007/s13361-019-02243-1.Peer-Reviewed Original Research
2018
Radio-sensitizing effects of VE-821 and beyond: Distinct phosphoproteomic and metabolomic changes after ATR inhibition in irradiated MOLT-4 cells
Šalovská B, Janečková H, Fabrik I, Karlíková R, Čecháková L, Ondrej M, Link M, Friedecký D, Tichý A. Radio-sensitizing effects of VE-821 and beyond: Distinct phosphoproteomic and metabolomic changes after ATR inhibition in irradiated MOLT-4 cells. PLOS ONE 2018, 13: e0199349. PMID: 30001349, PMCID: PMC6042708, DOI: 10.1371/journal.pone.0199349.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAtaxia Telangiectasia Mutated ProteinsBinding SitesBiomarkersCell Cycle CheckpointsCell Line, TumorComputational BiologyGamma RaysGene OntologyHumansMetabolomeMetabolomicsPhosphoproteinsPhosphorylationProtein BindingProtein Kinase InhibitorsProteomeProteomicsPyrazinesRadiation ToleranceRadiation-Sensitizing AgentsSignal TransductionSulfonesTOR Serine-Threonine KinasesConceptsVE-821MOLT-4 cellsCellular metabolismOncogene-induced replication stressATR inhibitionATM-deficient cellsDNA damage responseATR/Chk1 pathwayCell biology techniquesDownregulation of mTORAnti-cancer strategyCurrent anti-cancer strategiesReplication stressPhosphorylation sitesDamage responseIrradiation-induced oxidative stressQuantitative proteomicsDNA repairChk1 pathwayCellular eventsBiology techniquesSpecific inhibitorMain regulatorTumor-specific abnormalitiesMTOR inhibition
2015
Chemical inhibition of DNA repair kinases as a promising tool in oncology
Durisova K, Salovska B, Pejchal J, Tichy A. Chemical inhibition of DNA repair kinases as a promising tool in oncology. Biomedical Papers 2015, 160: 11-19. PMID: 26498210, DOI: 10.5507/bp.2015.046.Peer-Reviewed Original ResearchConceptsDNA-dependent protein kinaseDNA repair pathwaysRepair pathwaysDNA repairSpecific DNA repair pathwaysKey DNA repairDNA-damaging agentsSmall molecule inhibitorsATM-Rad3Protein kinaseAtaxia telangiectasiaChemical inhibitionKinaseMolecule inhibitorsSpecific inhibitorPathwayPotent inhibitorInhibitorsRecent studiesTumor resistanceTumor cellsMajor roleRadiotherapy efficiencyRepairCells
2014
Radiosensitization of Human Leukemic HL-60 Cells by ATR Kinase Inhibitor (VE-821): Phosphoproteomic Analysis
Šalovská B, Fabrik I, Ďurišová K, Link M, Vávrová J, Řezáčová M, Tichý A. Radiosensitization of Human Leukemic HL-60 Cells by ATR Kinase Inhibitor (VE-821): Phosphoproteomic Analysis. International Journal Of Molecular Sciences 2014, 15: 12007-12026. PMID: 25003641, PMCID: PMC4139827, DOI: 10.3390/ijms150712007.Peer-Reviewed Original ResearchConceptsDNA-dependent protein kinaseVE-821HL-60 cellsNano-liquid chromatography-tandem mass spectrometry analysisCell cycleSequence motif analysisDNA damage responseRadiation-induced double-strand breaksATR kinase inhibitorsDNA damage repairDNA damaging agentsHuman leukemic HL-60 cellsDouble-strand breaksSpecific ATR inhibitorActivity of kinasesInhibitor VE-821Leukemic HL-60 cellsCell cycle arrestQuantitative phosphoproteomicsATR kinaseMotif analysisPhosphorylation sitesCellular processesDamage responsePhosphoproteomic analysis
2013
Radio-sensitization of human leukaemic MOLT-4 cells by DNA-dependent protein kinase inhibitor, NU7441
Tichy A, Durisova K, Salovska B, Pejchal J, Zarybnicka L, Vavrova J, Dye N, Sinkorova Z. Radio-sensitization of human leukaemic MOLT-4 cells by DNA-dependent protein kinase inhibitor, NU7441. Radiation And Environmental Biophysics 2013, 53: 83-92. PMID: 24100951, DOI: 10.1007/s00411-013-0494-5.Peer-Reviewed Original ResearchConceptsDNA-dependent protein kinasePhosphorylation of H2A.XMOLT-4 cellsDNA-dependent protein kinase inhibitorDNA repair signalingProtein kinase inhibitorsAnti-apoptotic Mcl-1Cleavage of PARPHistone H2A.X.Cdc25A phosphataseProtein kinaseRepair signalingMolecular mechanismsNU7441Mcl-1Detection of IRDNA damageSpecific inhibitorPhosphorylationDetection of proteinsH2A.XSubsequent inductionKinase inhibitorsWestern blottingApoptosisDNA-dependent protein kinase and its inhibition in support of radiotherapy
Novotná E, Tichý A, Pejchal J, Lukášová E, Šalovská B, Vávrová J. DNA-dependent protein kinase and its inhibition in support of radiotherapy. International Journal Of Radiation Biology 2013, 89: 416-423. PMID: 23362996, DOI: 10.3109/09553002.2013.767993.Peer-Reviewed Original ResearchConceptsDNA-dependent protein kinaseRadiation-induced double strand break repairProtein kinaseDouble-strand break repairDNA repair proteinsDNA-PK inhibitionDNA-PK inhibitorKey DNA repair enzymeDNA repair enzymeBreak repairRepair proteinsPersonalized anti-cancer therapyRepair enzymesMolecular approachesMolecular mechanismsAnti-cancer therapyRecent discoveryCancer cellsKinaseRecent knowledgeRNASmall peptidesPivotal roleRecent studiesCancer therapy
2012
Radio-Sensitization of Human Leukaemic MOLT-4 Cells by DNA-Dependent Protein Kinase Inhibitor, NU7026
Tichý A, Novotná E, Ďurišová K, Šalovská B, Sedlaříková R, Pejchal J, Zárybnická L, Vávrová J, Šinkorová Z, Řezáčová M. Radio-Sensitization of Human Leukaemic MOLT-4 Cells by DNA-Dependent Protein Kinase Inhibitor, NU7026. Acta Medica 2012, 55: 66-73. PMID: 23101268, DOI: 10.14712/18059694.2015.57.Peer-Reviewed Original ResearchConceptsMOLT-4 cellsDNA repairDNA-dependent protein kinase inhibitorDNA-dependent protein kinaseDNA damage responsePost-translational modificationsCheckpoint kinase 2Protein kinase inhibitorsG2 phase arrestInduction of apoptosisATM kinaseDamage responseProtein kinaseKinase 2Cell cycle analysisNU7026Specific inhibitorCellular mechanismsPronounced apoptosisApoptosisKinase inhibitorsAmount of cellsCellsCycle analysisInhibitors
2011
Phosphoproteomics: Searching for a needle in a haystack
Tichy A, Salovska B, Rehulka P, Klimentova J, Vavrova J, Stulik J, Hernychova L. Phosphoproteomics: Searching for a needle in a haystack. Journal Of Proteomics 2011, 74: 2786-2797. PMID: 21839867, DOI: 10.1016/j.jprot.2011.07.018.Peer-Reviewed Original ResearchConceptsCharacterization of phosphoproteinsReversible phosphorylationCellular processesSignal transductionCell divisionNon-phosphorylated peptidesGene expressionInsufficient ionizationLow abundanceTryptic protein digestsMass spectrometryCritical roleProtein digestsEnrichment techniquePhosphoproteomePhosphoproteomicsPhosphoproteinPowerful toolTransductionPhosphorylationPhosphopeptidesProteinAbundanceApoptosisDifferentiation