2025
The mitotic ATR-Chk1 pathway promotes CDK1 activity for faithful chromosome segregation.
Joo YK, Parrado CR, Li W, Yang R, Black E, Bleichert F, Liu Y, Kabeche L. The mitotic ATR-Chk1 pathway promotes CDK1 activity for faithful chromosome segregation. Cell Rep 2025, 44: 116019. PMID: 40705605, DOI: 10.1016/j.celrep.2025.116019.Peer-Reviewed Original ResearchA robust multiplex-DIA workflow profiles protein turnover regulations associated with cisplatin resistance and aneuploidy
Salovska B, Li W, Bernhardt O, Germain P, Wang Q, Gandhi T, Reiter L, Liu Y. A robust multiplex-DIA workflow profiles protein turnover regulations associated with cisplatin resistance and aneuploidy. Nature Communications 2025, 16: 5034. PMID: 40447611, PMCID: PMC12125295, DOI: 10.1038/s41467-025-60319-x.Peer-Reviewed Original ResearchConceptsMS platformsMass spectrometryDrug discoveryCisplatin resistanceDegradation kineticsDegradation profileAssociated with cisplatin resistanceProtein turnoverLabeled channelsProtein complex subunitsRespiratory complex IMitochondrial metabolic adaptationRobust workflowProtein degradation profilesCancer cell modelsMeasure protein turnoverProtein turnover regulationProteome dynamicsSpectrometryHigh-throughputComplex ICellular processesComplex subunitsSILAC labelingAneuploid genomesCrystal structure of Isthmin-1 and reassessment of its functional role in pre-adipocyte signaling
Li T, Stayrook S, Li W, Wang Y, Li H, Zhang J, Liu Y, Klein D. Crystal structure of Isthmin-1 and reassessment of its functional role in pre-adipocyte signaling. Nature Communications 2025, 16: 3580. PMID: 40234450, PMCID: PMC12000326, DOI: 10.1038/s41467-025-58828-w.Peer-Reviewed Original ResearchConceptsThrombospondin type I repeatsIsthmin-1Pre-adipocytesType I repeatsBacterial streptavidinSurface helicesI repeatsMolecular detailsDiverse functionsFunctional studiesAkt phosphorylationFunctional roleStructural plasticityInsulin-like propertiesCrystal structureAMOPGrowth factorDomainPhosphorylationApoptosisLiver steatosisProteinHelixAktStreptavidinOnline Alkaline-pH Reversed-Phase Nanoelectrospray-Tandem Mass Spectrometry Complements Traditional Phosphoproteomic Analysis via Influencing Charge State Distribution of Phosphopeptides
Wang Y, Gao J, Xie W, Tang M, Chen X, Chen L, Chen H, Yang Z, Gao Q, Liu Y, Zhou H. Online Alkaline-pH Reversed-Phase Nanoelectrospray-Tandem Mass Spectrometry Complements Traditional Phosphoproteomic Analysis via Influencing Charge State Distribution of Phosphopeptides. Journal Of Proteome Research 2025, 24: 2443-2453. PMID: 40205994, DOI: 10.1021/acs.jproteome.4c01091.Peer-Reviewed Original ResearchConceptsNanoelectrospray tandem mass spectrometryPhosphopeptide enrichment techniquesNanoelectrospray ionizationTandem MSMass spectrometerC18 columnNormal adjacent tissuesMass spectrometryPairs of hepatocellular carcinomaPhosphorylated peptidesLiquid chromatography fractionationPhosphopeptidesHigh pHActual polarizationBiological functionsPhosphoproteomic analysisChromatography fractionsIonizationSpectrometryLow pHEnrichment techniquesHepatocellular carcinomaSpectrometerAdjacent tissuesGlobal phosphorylationAn in vivo screen identifies NAT10 as a master regulator of brain metastasis
Chen J, Xu P, Cai W, Chen H, Wingrove E, Shi X, Li W, Biancon G, Zhang M, Balabaki A, Krop E, Asare E, Zhang Y, Yin M, Tebaldi T, Meier J, Westbrook T, Halene S, Liu Y, Shen H, Nguyen D, Yan Q. An in vivo screen identifies NAT10 as a master regulator of brain metastasis. Science Advances 2025, 11: eads6021. PMID: 40138393, PMCID: PMC11939035, DOI: 10.1126/sciadv.ads6021.Peer-Reviewed Original ResearchConceptsPhosphoserine aminotransferase 1Metastasis in vivoIn vivo screeningRNA helicase domainRegulator of brain metastasisMetastatic breast cancer cellsBrain metastasis in vivoBrain metastasesRNA helicaseCell growth in vitroBreast cancer cellsCancer cell proliferationSerine biosynthesisEpigenetic regulationGrowth in vitroNAT10Migration in vitroCancer cellsTumor growthCell proliferationPrimary tumor growthDrivers of brain metastasesRNACancer metastasisCancer-related deathsTurnover atlas of proteome and phosphoproteome across mouse tissues and brain regions
Li W, Dasgupta A, Yang K, Wang S, Hemandhar-Kumar N, Chepyala S, Yarbro J, Hu Z, Salovska B, Fornasiero E, Peng J, Liu Y. Turnover atlas of proteome and phosphoproteome across mouse tissues and brain regions. Cell 2025, 188: 2267-2287.e21. PMID: 40118046, PMCID: PMC12033170, DOI: 10.1016/j.cell.2025.02.021.Peer-Reviewed Original ResearchConceptsMouse tissuesNeurodegeneration-related proteinsPost-translational modificationsImpact of phosphorylationStable isotope labelingLong-lived proteinsPeroxisomal proteinsProtein lifetimeProteomic propertiesProtein phosphorylationProtein stabilityInteractive web-based portalProtein abundanceProtein turnoverPhosphorylationMammalian tissuesComprehensive resourceProteinIsotope labelingProteomicsA-synucleinAbundanceTurnoverTurnover changesPhosphositesMass spectrometry-based mapping of plasma protein QTLs in children and adolescents
Liu Y. Mass spectrometry-based mapping of plasma protein QTLs in children and adolescents. Nature Genetics 2025, 57: 487-488. PMID: 39972213, DOI: 10.1038/s41588-025-02088-3.Peer-Reviewed Original ResearchHuman and mouse proteomics reveals the shared pathways in Alzheimer’s disease and delayed protein turnover in the amyloidome
Yarbro J, Han X, Dasgupta A, Yang K, Liu D, Shrestha H, Zaman M, Wang Z, Yu K, Lee D, Vanderwall D, Niu M, Sun H, Xie B, Chen P, Jiao Y, Zhang X, Wu Z, Chepyala S, Fu Y, Li Y, Yuan Z, Wang X, Poudel S, Vagnerova B, He Q, Tang A, Ronaldson P, Chang R, Yu G, Liu Y, Peng J. Human and mouse proteomics reveals the shared pathways in Alzheimer’s disease and delayed protein turnover in the amyloidome. Nature Communications 2025, 16: 1533. PMID: 39934151, PMCID: PMC11814087, DOI: 10.1038/s41467-025-56853-3.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseProtein turnoverMouse model of amyloidosisMulti-omics analysisMurine model of Alzheimer's diseaseModel of Alzheimer's diseaseModel of amyloidosisProteome turnoverMouse proteomeGenetic incorporationAD pathwayAmyloid formationBrain proteomeMulti-OmicsProteomic strategyAD progressionProteomicsProtein alterationsProteinDisease mechanismsAmyloidPathwayPotential targetMouse brainTurnoverAdvancing Scientific Communication in Proteomics
Searle B, Chazarin B, Collins B, Kundu D, Huang S, Lin Q, Liu Y, Low T, Saba J, Guo T, Palmisano G, Fert-Bober J. Advancing Scientific Communication in Proteomics. Journal Of Proteome Research 2025, 24: 381-382. PMID: 39916559, DOI: 10.1021/acs.jproteome.4c01098.Peer-Reviewed Original Research
2024
Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation
Black E, Ramírez Parrado C, Trier I, Li W, Joo Y, Pichurin J, Liu Y, Kabeche L. Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation. Nature Communications 2024, 15: 10782. PMID: 39737931, PMCID: PMC11685634, DOI: 10.1038/s41467-024-54922-7.Peer-Reviewed Original ResearchConceptsPolo-like kinase 1Plk1 activityChromosome segregationMitotic polo-like kinase 1Mitotic chromosome segregationProtecting genome stabilitySensitivity to PLK1 inhibitorsMitotic cell divisionCheckpoint kinase 2Polo-like kinase 1 activityDNA damage repairGenome stabilityChromosome missegregationCytokinetic defectsCell divisionGenomic instabilityT-loopCell cycleKinase activityChromosome misalignmentMitotic errorsChk2Kinase 2Damage repairChromosomeAuthor Correction: π-HuB: the proteomic navigator of the human body
He F, Aebersold R, Baker M, Bian X, Bo X, Chan D, Chang C, Chen L, Chen X, Chen Y, Cheng H, Collins B, Corrales F, Cox J, E W, Van Eyk J, Fan J, Faridi P, Figeys D, Gao G, Gao W, Gao Z, Goda K, Goh W, Gu D, Guo C, Guo T, He Y, Heck A, Hermjakob H, Hunter T, Iyer N, Jiang Y, Jimenez C, Joshi L, Kelleher N, Li M, Li Y, Lin Q, Liu C, Liu F, Liu G, Liu Y, Liu Z, Low T, Lu B, Mann M, Meng A, Moritz R, Nice E, Ning G, Omenn G, Overall C, Palmisano G, Peng Y, Pineau C, Poon T, Purcell A, Qiao J, Reddel R, Robinson P, Roncada P, Sander C, Sha J, Song E, Srivastava S, Sun A, Sze S, Tang C, Tang L, Tian R, Vizcaíno J, Wang C, Wang C, Wang X, Wang X, Wang Y, Weiss T, Wilhelm M, Winkler R, Wollscheid B, Wong L, Xie L, Xie W, Xu T, Xu T, Yan L, Yang J, Yang X, Yates J, Yun T, Zhai Q, Zhang B, Zhang H, Zhang L, Zhang L, Zhang P, Zhang Y, Zheng Y, Zhong Q, Zhu Y. Author Correction: π-HuB: the proteomic navigator of the human body. Nature 2024, 637: e22-e22. PMID: 39715925, DOI: 10.1038/s41586-024-08555-x.Peer-Reviewed Original Researchπ-HuB: the proteomic navigator of the human body
He F, Aebersold R, Baker M, Bian X, Bo X, Chan D, Chang C, Chen L, Chen X, Chen Y, Cheng H, Collins B, Corrales F, Cox J, E W, Van Eyk J, Fan J, Faridi P, Figeys D, Gao G, Gao W, Gao Z, Goda K, Goh W, Gu D, Guo C, Guo T, He Y, Heck A, Hermjakob H, Hunter T, Iyer N, Jiang Y, Jimenez C, Joshi L, Kelleher N, Li M, Li Y, Lin Q, Liu C, Liu F, Liu G, Liu Y, Liu Z, Low T, Lu B, Mann M, Meng A, Moritz R, Nice E, Ning G, Omenn G, Overall C, Palmisano G, Peng Y, Pineau C, Poon T, Purcell A, Qiao J, Reddel R, Robinson P, Roncada P, Sander C, Sha J, Song E, Srivastava S, Sun A, Sze S, Tang C, Tang L, Tian R, Vizcaíno J, Wang C, Wang C, Wang X, Wang X, Wang Y, Weiss T, Wilhelm M, Winkler R, Wollscheid B, Wong L, Xie L, Xie W, Xu T, Xu T, Yan L, Yang J, Yang X, Yates J, Yun T, Zhai Q, Zhang B, Zhang H, Zhang L, Zhang L, Zhang P, Zhang Y, Zheng Y, Zhong Q, Zhu Y. π-HuB: the proteomic navigator of the human body. Nature 2024, 636: 322-331. PMID: 39663494, DOI: 10.1038/s41586-024-08280-5.Peer-Reviewed Original ResearchGABAA receptor π forms channels that stimulate ERK through a G-protein-dependent pathway
Wang Y, Zhang Y, Li W, Salovska B, Zhang J, Li T, Li H, Liu Y, Kaczmarek L, Pusztai L, Klein D. GABAA receptor π forms channels that stimulate ERK through a G-protein-dependent pathway. Molecular Cell 2024, 85: 166-176.e5. PMID: 39642883, PMCID: PMC11698630, DOI: 10.1016/j.molcel.2024.11.016.Peer-Reviewed Original ResearchExtracellular regulated kinaseStimulated extracellular regulated kinaseExtracellular-regulated kinase signalingG-protein-dependent pathwayG protein-coupled pathwayUncharacterized pathwayGrowth signalsSignaling functionsCryoelectron microscopyCryo-EMSignaling mechanismsGABRPFunctional assaysNative nanodiscsPathwayStimulate growthPhysiological concentrationsAbsence of GABATargeted inhibitionType A receptorConcentrations of GABAMetabotropic receptorsIonotropic activitySignalGABA bindingA proteome-wide quantitative platform for nanoscale spatially resolved extraction of membrane proteins into native nanodiscs
Brown C, Ghosh S, McAllister R, Kumar M, Walker G, Sun E, Aman T, Panda A, Kumar S, Li W, Coleman J, Liu Y, Rothman J, Bhattacharyya M, Gupta K. A proteome-wide quantitative platform for nanoscale spatially resolved extraction of membrane proteins into native nanodiscs. Nature Methods 2024, 22: 412-421. PMID: 39609567, PMCID: PMC11810782, DOI: 10.1038/s41592-024-02517-x.Peer-Reviewed Original ResearchTarget membrane proteinsMembrane proteinsMembrane contextSynaptic vesicle membrane proteinVesicle membrane proteinsMammalian membrane proteinsMembrane-active polymersExtraction of membrane proteinsNative nanodiscsOrganellar membranesNative membrane environmentMultiprotein complexesMolecular contextCellular membranesMembrane environmentQuantitative platformBioanalytical approachesExtraction efficiencyOpen-access databasesProteinMembraneExtraction conditionsNanodiscsTarget MPA proteogenomic analysis of cervical cancer reveals therapeutic and biological insights
Yu J, Gui X, Zou Y, Liu Q, Yang Z, An J, Guo X, Wang K, Guo J, Huang M, Zhou S, Zuo J, Chen Y, Deng L, Yuan G, Li N, Song Y, Jia J, Zeng J, Zhao Y, Liu X, Du X, Liu Y, Wang P, Zhang B, Ding L, Robles A, Rodriguez H, Zhou H, Shao Z, Wu L, Gao D. A proteogenomic analysis of cervical cancer reveals therapeutic and biological insights. Nature Communications 2024, 15: 10114. PMID: 39578447, PMCID: PMC11584810, DOI: 10.1038/s41467-024-53830-0.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAdultBiomarkers, TumorCell Line, TumorCell ProliferationE1A-Associated p300 ProteinFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedPapillomaviridaePapillomavirus InfectionsPrognosisProtein Kinase C betaProtein Processing, Post-TranslationalProteogenomicsProto-Oncogene Proteins c-fosUterine Cervical NeoplasmsConceptsCervical cancerIncidence of cervical cancerIntegrative proteogenomic analysisMulti-omic changesHuman papillomavirusImmune infiltrationSignificant public health issueProteogenomic analysisGenetic alterationsCC patientsPatient subgroupsMalignant proliferationAnalysis of cervical cancerCC tumorsChinese womenPost-translational modifications regulationPublic health issuePotential treatmentScreening strategiesClinical practiceProliferation of CC cellsPatientsWomen's healthCancerLow-income countriesPTMoreR-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 speciesPTMProteomicsKinaseMammalsProteinMultiscale modeling uncovers 7q11.23 copy number variation–dependent changes in ribosomal biogenesis and neuronal maturation and excitability
Mihailovich M, Germain P, Shyti R, Pozzi D, Noberini R, Liu Y, Aprile D, Tenderini E, Troglio F, Trattaro S, Fabris S, Ciptasari U, Rigoli M, Caporale N, D’Agostino G, Mirabella F, Vitriolo A, Capocefalo D, Skaros A, Franchini A, Ricciardi S, Biunno I, Neri A, Kasri N, Bonaldi T, Aebersold R, Matteoli M, Testa G. Multiscale modeling uncovers 7q11.23 copy number variation–dependent changes in ribosomal biogenesis and neuronal maturation and excitability. Journal Of Clinical Investigation 2024, 134: e168982. PMID: 39007270, PMCID: PMC11245157, DOI: 10.1172/jci168982.Peer-Reviewed Original ResearchConceptsCopy number variationsWilliams-Beuren syndromeRibosome biogenesisP-RPS6Neurodevelopmental disordersRibosomal genesP-4EBPNumber variationsTranslation factorsMicroduplication syndromeMolecular mechanismsGenesNeuronal differentiationPatient-derivedIntrinsic excitabilityMTOR pathwayBiogenesisNeuronal maturationPhosphorylated rpS6Neuronal transmissionWilliams-BeurenPathophysiological relevanceNeurocognitive featuresIntellectual disabilityDisease modelsNetwork-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 mediumFibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury
Gui Y, Fu H, Palanza Z, Tao J, Lin Y, Min W, Qiao Y, Bonin C, Hargis G, Wang Y, Yang P, Kreutzer D, Wang Y, Liu Y, Yu Y, Liu Y, Zhou D. Fibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury. Journal Of Clinical Investigation 2024, 134: e165836. PMID: 38713523, PMCID: PMC11213467, DOI: 10.1172/jci165836.Peer-Reviewed Original ResearchNidogen-1Expression of transmembrane proteinsCell-matrix interactionsAcute kidney injuryExtracellular matrix proteinsWnt Signaling PathwayGlobal proteomeHedgehog signalingTransmembrane proteinsTubular cell apoptosisSignaling pathwayCell apoptosisMatrix proteinsIntegrin B1Kidney fibroblastsMesenchymal cell activationKidney injuryHedgehogProteinMitigate acute kidney injurySMOPreserved kidney functionAcute kidney injury pathogenesisFibroblastsPhosphoproteomeReciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry
Ke S, Dang F, Wang L, Chen J, Naik M, Li W, Thavamani A, Kim N, Naik N, Sui H, Tang W, Qiu C, Koikawa K, Batalini F, Stern Gatof E, Isaza D, Patel J, Wang X, Clohessy J, Heng Y, Lahav G, Liu Y, Gray N, Zhou X, Wei W, Wulf G, Lu K. Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry. Nature Communications 2024, 15: 3220. PMID: 38622115, PMCID: PMC11018817, DOI: 10.1038/s41467-024-47427-w.Peer-Reviewed Original ResearchConceptsCyclin-dependent protein kinasesCell cycle entryMitotic proteinsProtein stabilityActivator of anaphase-promoting complexPermanent cell cycle exitAnaphase-promoting complexE3 ligase activityCo-activator Cdh1Cell cycle exitLigase activityPositive feedback loopProlyl isomerizationProteomic screenProtein kinaseCycle entryProtein turnoverPin1Oncoprotein degradationCo-activationAPC/CCdh1Pin1 inhibitionTriple-negative breast cancerProteinPhosphorylation
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