Featured Publications
An 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 ResearchMeSH KeywordsEndothelial CellsHumansOptogeneticsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktSignal TransductionConceptsPhosphorylation 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 ResearchMeSH KeywordsAntineoplastic AgentsColorectal NeoplasmsDiabetes Mellitus, Type 2HumansMetforminSignal TransductionConceptsColorectal 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 therapeuticsGlobal 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
2024
Network-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 ResearchMeSH KeywordsApoptosisCell Line, TumorErbB ReceptorsHumansPhosphorylationProteolysis Targeting ChimeraSignal TransductionTyrosineConceptsInhibit 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
2021
A PKD-MFF signaling axis couples mitochondrial fission to mitotic progression
Pangou E, Bielska O, Guerber L, Schmucker S, Agote-Arán A, Ye T, Liao Y, Puig-Gamez M, Grandgirard E, Kleiss C, Liu Y, Compe E, Zhang Z, Aebersold R, Ricci R, Sumara I. A PKD-MFF signaling axis couples mitochondrial fission to mitotic progression. Cell Reports 2021, 35: 109129. PMID: 34010649, DOI: 10.1016/j.celrep.2021.109129.Peer-Reviewed Original ResearchConceptsMitochondrial fission factorProtein kinase DMitochondrial fissionMitotic progressionMFF-dependent mitochondrial fissionGenome integrityChromosome segregationDynamic organellesKinase DMitochondrial receptorDaughter cellsFission factorMammalian cellsMitotic checkpointCell divisionFusion eventsInterphasic cellsCell survivalProtein 1PhosphorylationMitochondriaCellsFissionDynaminOrganellesCross-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 ResearchMeSH KeywordsCell Cycle ProteinsMitosisProtein Tyrosine PhosphatasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSignal Transduction
2017
Systematic proteome and proteostasis profiling in human Trisomy 21 fibroblast cells
Liu Y, Borel C, Li L, Müller T, Williams EG, Germain PL, Buljan M, Sajic T, Boersema PJ, Shao W, Faini M, Testa G, Beyer A, Antonarakis SE, Aebersold R. Systematic proteome and proteostasis profiling in human Trisomy 21 fibroblast cells. Nature Communications 2017, 8: 1212. PMID: 29089484, PMCID: PMC5663699, DOI: 10.1038/s41467-017-01422-6.Peer-Reviewed Original ResearchConceptsSWATH mass spectrometryPost-transcriptional effectsMitochondrial proteomeProteome remodelingProteomic resourceTranscriptomic dataProteomic dataProtein abundanceProtein turnoverEntire chromosome 21ProteomeProtein expressionPhenotypic manifestationsChromosome 21Fibroblast cellsStoichiometric complexSignificant downregulationMonozygotic twin pair discordantTwin pair discordantMass spectrometryMajor determinantChromosomesProteinPair discordantAbundance