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 inhibitors
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 therapeutics
2022
Human 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 concentrationData-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 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 acidTurnoverNAguideR: performing and prioritizing missing value imputations for consistent bottom-up proteomic analyses
Wang S, Li W, Hu L, Cheng J, Yang H, Liu Y. NAguideR: performing and prioritizing missing value imputations for consistent bottom-up proteomic analyses. Nucleic Acids Research 2020, 48: e83-e83. PMID: 32526036, PMCID: PMC7641313, DOI: 10.1093/nar/gkaa498.Peer-Reviewed Original ResearchIsoform‐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
motifeR: An Integrated Web Software for Identification and Visualization of Protein Posttranslational Modification Motifs
Wang S, Cai Y, Cheng J, Li W, Liu Y, Yang H. motifeR: An Integrated Web Software for Identification and Visualization of Protein Posttranslational Modification Motifs. Proteomics 2019, 19: e1900245. PMID: 31622013, DOI: 10.1002/pmic.201900245.Peer-Reviewed Original ResearchConceptsUser-friendly web toolWeb softwarePublic datasetsBioinformatics backgroundLarge datasetsWeb toolMotif discoveryOptional featuresDatasetPresentation of motivesExponential growthLocation probabilitySoftwareKinase-substrate relationsModification sitesProtein post-translational modificationsPost-translational modificationsUsabilityUsersToolToolkitNetworkModification motifsPhosphoproteomic datasetsSite enrichmentCombining 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 acquisitionAssessing 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