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 speciesPTMProteomicsKinaseMammalsProteinNetwork-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis
Rosenberger G, Li W, Turunen M, He J, Subramaniam P, Pampou S, Griffin A, Karan C, Kerwin P, Murray D, Honig B, Liu Y, Califano A. Network-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis. Nature Communications 2024, 15: 3909. PMID: 38724493, PMCID: PMC11082183, DOI: 10.1038/s41467-024-47957-3.Peer-Reviewed Original ResearchConceptsMechanism of cell responseResistance mechanismsSignaling pathway responsesDrug resistance mechanismsEnzyme/substrate interactionsAdaptive resistance mechanismsNetwork rewiringPhosphorylation stateSignaling pathway activationDrug perturbationsProteomic technologiesSignaling crosstalkPathway responsesInhibitor designPathway activationCancer drug resistance mechanismsCell adaptive responsesAdaptive responsePhosphatase activityNetwork-based methodologyRewiringTherapeutic efficacyPhosphoproteome coverageCell responsesControl mediumEGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling
Hu Z, Chen P, Li W, Krone M, Zheng S, Saarbach J, Velasco I, Hines J, Liu Y, Crews C. EGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling. Science Advances 2024, 10: eadj7251. PMID: 38536914, PMCID: PMC10971414, DOI: 10.1126/sciadv.adj7251.Peer-Reviewed Original ResearchConceptsInhibit cancer cell viabilityProteome-wide levelCancer cell viabilityDifferential signaling pathwaysPhosphoproteomic approachTyrosine dephosphorylationProtein dephosphorylationSignal transductionActivating dephosphorylationInduce apoptosisReceptor tyrosine kinase inhibitorsRTK activationSignaling pathwayInhibition of kinasesDephosphorylationEpidermal growth factor receptorGrowth factor receptorCell viabilityFactor receptorInhibitory approachesTyrosineTyrosine kinase inhibitorsInhibitory effectInhibitory potentialKinase inhibitorsThe CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells
Liao X, Li W, Zhou H, Rajendran B, Li A, Ren J, Luan Y, Calderwood D, Turk B, Tang W, Liu Y, Wu D. The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells. Nature Communications 2024, 15: 603. PMID: 38242867, PMCID: PMC10798966, DOI: 10.1038/s41467-024-44885-0.Peer-Reviewed Original ResearchConceptsCD8+ T cellsT cellsCancer immunotherapyMouse CD8+ T cellsAnti-tumor immunityTumor growth inhibition abilityAnti-tumor effectsInhibition of neddylationCD8Effector functionsTCR stimulationIL2 signalingCentral signaling pathwaysCore signaling pathwaysEffector activityNegative regulatory mechanismsTranslational implicationsImmunotherapyGrowth inhibition abilityCytokine signalingTCRProteomic alterationsSignaling pathwayCancerCRISPR-based screens
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 factorAktCells7SK methylation by METTL3 promotes transcriptional activity
Perez-Pepe M, Desotell A, Li H, Li W, Han B, Lin Q, Klein D, Liu Y, Goodarzi H, Alarcón C. 7SK methylation by METTL3 promotes transcriptional activity. Science Advances 2023, 9: eade7500. PMID: 37163588, PMCID: PMC10171809, DOI: 10.1126/sciadv.ade7500.Peer-Reviewed Original ResearchConceptsTranscriptional elongationTranscriptional responseAdaptive transcriptional responseHeterogeneous nuclear ribonucleoproteinsElongation factor complexPositive transcription elongation factor complexGrowth factorExtracellular signalsRNA modificationsRNA 7SKEpidermal growth factorCell signalingInduces phosphorylationMethyltransferase 3Nuclear ribonucleoproteinFactor complexTranscriptional activityUnknown functionMethylationMETTL3RibonucleoproteinPhosphorylationTEFbElongationSignalingPhosphoproteomic 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 therapeuticsTargeted Dephosphorylation of Tau by Phosphorylation Targeting Chimeras (PhosTACs) as a Therapeutic Modality
Hu Z, Chen P, Li W, Douglas T, Hines J, Liu Y, Crews C. Targeted Dephosphorylation of Tau by Phosphorylation Targeting Chimeras (PhosTACs) as a Therapeutic Modality. Journal Of The American Chemical Society 2023, 145: 4045-4055. PMID: 36753634, DOI: 10.1021/jacs.2c11706.Peer-Reviewed Original ResearchProtein tauTau dephosphorylationDisease-modifying therapiesMicrotubule-associated protein tauTau phosphorylation levelsImportant pathological roleTherapeutic modalitiesTau phosphorylationAlzheimer's diseaseTau proteinTherapeutic potentialPathological roleKinase inhibitorsEnhanced downregulationLimited benefitPhosphorylation levelsTauTauopathiesDiseaseCurrent strategiesTau phosphataseA basic phosphoproteomic-DIA workflow integrating precise quantification of phosphosites in systems biology
Di Y, Li W, Salovska B, Ba Q, Hu Z, Wang S, Liu Y. A basic phosphoproteomic-DIA workflow integrating precise quantification of phosphosites in systems biology. Biophysics Reports 2023, 9: 82-98. PMID: 37753060, PMCID: PMC10518521, DOI: 10.52601/bpr.2023.230007.Peer-Reviewed Original ResearchPost-translational modificationsData-independent acquisitionSystems biologySite-specific phosphorylation eventsImportant post-translational modificationMost human proteinsCritical protein functionsPhosphorylation eventsProtein functionPhosphoproteomic studiesPhosphoproteomic analysisBioinformatics AdvancesHuman proteinsMass spectrometry technologyBioinformatics analysisLarge-scale quantificationExperimental workflowHigh-resolution mass spectrometry technologySpectrometry technologyPhosphoproteomicsPhosphorylationBiologyProteinSystems medicineSingle experiment
2022
Toward a hypothesis‐free understanding of how phosphorylation dynamically impacts protein turnover
Li W, Salovska B, Fornasiero E, Liu Y. Toward a hypothesis‐free understanding of how phosphorylation dynamically impacts protein turnover. Proteomics 2022, 23: e2100387. PMID: 36422574, PMCID: PMC10964180, DOI: 10.1002/pmic.202100387.Peer-Reviewed Original ResearchConceptsPost-translational modificationsProtein turnoverDynamic stable isotope labelingCell starvationStable isotope labelingData-independent acquisition mass spectrometryAcquisition mass spectrometryProteome levelTurnover diversityPhosphoproteomic datasetsPhosphorylation stoichiometryMetabolic labelingIsotope labelingMass spectrometryPhosphorylationAmino acidsCell culturesBiological perspectiveStarvationTurnoverTurnover measurementsRecent studiesSILACProteoformsPeptidoformsProteotype coevolution and quantitative diversity across 11 mammalian species
Ba Q, Hei Y, Dighe A, Li W, Maziarz J, Pak I, Wang S, Wagner GP, Liu Y. Proteotype coevolution and quantitative diversity across 11 mammalian species. Science Advances 2022, 8: eabn0756. PMID: 36083897, PMCID: PMC9462687, DOI: 10.1126/sciadv.abn0756.Peer-Reviewed Original ResearchConceptsMammalian speciesRNA metabolic processesCommon mammalian speciesUbiquitin-proteasome systemEvolutionary profilingMammalian lineagesProteomic methodsProtein degradationProtein abundanceGene expressionProtein expression levelsHigh interspeciesMetabolic processesCovariation analysisFunctional roleNucleotide levelExpression levelsQuantitative diversityCoevolutionMammalsSpeciesRemarkable variationExpressionTranscriptomeBiological variabilityHuman WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation
Cai WL, Chen JF, Chen H, Wingrove E, Kurley SJ, Chan LH, Zhang M, Arnal-Estape A, Zhao M, Balabaki A, Li W, Yu X, Krop ED, Dou Y, Liu Y, Jin J, Westbrook TF, Nguyen DX, Yan Q. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation. ELife 2022, 11: e78163. PMID: 36043466, PMCID: PMC9584608, DOI: 10.7554/elife.78163.Peer-Reviewed Original ResearchConceptsBreast cancer cellsMetastatic breast cancerBreast cancerRibosomal gene expressionCancer cellsKnockdown of WDR5Vivo genetic screenReversible epigenetic mechanismsGenetic screenTranslation regulationTriple-negative breast cancerEpigenetic regulatorsEpigenetic mechanismsBreast cancer growthCancer-related deathTranslation efficiencyWDR5Novel therapeutic strategiesTranslation rateGene expressionCell growthAdvanced diseaseEffective therapyMetastatic capabilityPotent suppression
2021
MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells
Jeong J, Shin JH, Li W, Hong JY, Lim J, Hwang JY, Chung JJ, Yan Q, Liu Y, Choi J, Wysolmerski J. MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells. Cell Reports 2021, 37: 110160. PMID: 34965434, PMCID: PMC8762588, DOI: 10.1016/j.celrep.2021.110160.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBreast NeoplasmsCell ProliferationCytoskeletal ProteinsDrug Resistance, NeoplasmEndocytosisFemaleHumansMembrane MicrodomainsMyelin and Lymphocyte-Associated Proteolipid ProteinsPhosphoproteinsPlasma Membrane Calcium-Transporting ATPasesReceptor, ErbB-2Sodium-Hydrogen ExchangersTrastuzumabTumor Cells, CulturedConceptsLipid raft formationBreast cancer cellsLipid raftsLipid raft resident proteinsCancer cellsRaft formationRaft-resident proteinsProximity ligation assayProtein complexesMembrane protrusionsProtein interactionsPlasma membraneLigation assayMAL2Membrane stabilityStructural organizationPotential therapeutic targetPhysical interactionMembrane retentionProteinRaftsTherapeutic targetCellsIntracellular calcium concentrationLow intracellular calcium concentrationDeveloping a Bimolecular Affinity Purification Strategy to Isolate 26S Proteasome Holocomplexes for Complex-Centric Proteomic Analysis
Yu C, Wang X, Li W, Liu Y, Huang L. Developing a Bimolecular Affinity Purification Strategy to Isolate 26S Proteasome Holocomplexes for Complex-Centric Proteomic Analysis. Analytical Chemistry 2021, 93: 13407-13413. PMID: 34550675, PMCID: PMC8999942, DOI: 10.1021/acs.analchem.1c03551.Peer-Reviewed Original ResearchData-independent acquisition-based proteome and phosphoproteome profiling across six melanoma cell lines reveals determinants of proteotypes
Gao E, Li W, Wu C, Shao W, Di Y, Liu Y. Data-independent acquisition-based proteome and phosphoproteome profiling across six melanoma cell lines reveals determinants of proteotypes. Molecular Omics 2021, 17: 413-425. PMID: 33728422, PMCID: PMC8205956, DOI: 10.1039/d0mo00188k.Peer-Reviewed Original ResearchBoxCarmax: A High-Selectivity Data-Independent Acquisition Mass Spectrometry Method for the Analysis of Protein Turnover and Complex Samples
Salovska B, Li W, Di Y, Liu Y. BoxCarmax: A High-Selectivity Data-Independent Acquisition Mass Spectrometry Method for the Analysis of Protein Turnover and Complex Samples. Analytical Chemistry 2021, 93: 3103-3111. PMID: 33533601, PMCID: PMC8959401, DOI: 10.1021/acs.analchem.0c04293.Peer-Reviewed Original ResearchConceptsData-independent acquisitionProtein turnoverDIA mass spectrometryStable isotope labelingValuable biological insightsRelative protein quantificationSerum starvation stressIsotopic labeling approachSILAC experimentsStarvation stressConventional DIA methodGas-phase separation strategyBiological insightsDegradation regulationIsotope labelingCultured cellsAmino acidsDIA-MSProtein quantificationLabeling approachPeptide pairsCell culturesBiological investigationsMultiplexed acquisitionComplex samplesCross-compartment signal propagation in the mitotic exit network
Zhou X, Li W, Liu Y, Amon A. Cross-compartment signal propagation in the mitotic exit network. ELife 2021, 10: e63645. PMID: 33481703, PMCID: PMC7822594, DOI: 10.7554/elife.63645.Peer-Reviewed Original Research
2020
FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho
Suzuki Y, Kuzina E, An SJ, Tome F, Mohanty J, Li W, Lee S, Liu Y, Lax I, Schlessinger J. FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 31800-31807. PMID: 33257569, PMCID: PMC7749347, DOI: 10.1073/pnas.2018554117.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCalcinosisCell MembraneFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseHEK293 CellsHumansHyperostosis, Cortical, CongenitalHyperphosphatemiaImmunoglobulin Fc FragmentsKlotho ProteinsMutationOsteomalaciaProtein BindingProtein DomainsProtein MultimerizationRecombinant Fusion ProteinsRickets, HypophosphatemicConceptsFGF receptorsTotal internal reflection fluorescence microscopyChimeric receptor moleculesReflection fluorescence microscopyBinding sitesDisulfide bridge formationCritical metabolic processesMAPK responseCytoplasmic domainGrowth factor familyTerminal tailFactor familyKinase activationSimilar binding affinitiesExtracellular domainFGFR1 activationTandem repeatsMetabolic processesDisulfide bridgesCell surfaceDistinct ligandsCell membraneFluorescence microscopyDistinct high-affinity binding sitesPhosphate homeostasisGlobal 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 acidTurnover