2023
MAD2-Dependent Insulin Receptor Endocytosis Regulates Metabolic Homeostasis.
Park J, Hall C, Hubbard B, LaMoia T, Gaspar R, Nasiri A, Li F, Zhang H, Kim J, Haeusler R, Accili D, Shulman G, Yu H, Choi E. MAD2-Dependent Insulin Receptor Endocytosis Regulates Metabolic Homeostasis. Diabetes 2023, 72: 1781-1794. PMID: 37725942, PMCID: PMC10658066, DOI: 10.2337/db23-0314.Peer-Reviewed Original ResearchConceptsIR endocytosisInsulin receptor endocytosisCell division regulatorsInsulin receptorProlongs insulin actionReceptor endocytosisTranscriptomic profilesInsulin stimulationEndocytosisMetabolic homeostasisCell surfaceGenetic ablationMetabolic functionsInsulin actionP31cometMad2BubR1DisruptionSignalingRegulatorHomeostasisAdipose tissueInteractionHepatic fat accumulationMetabolismMulti-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells
Wang Y, Popovic Z, Charkoftaki G, Garcia-Milian R, Lam T, Thompson D, Chen Y, Vasiliou V. Multi-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells. Chemico-Biological Interactions 2023, 384: 110714. PMID: 37716420, PMCID: PMC10807983, DOI: 10.1016/j.cbi.2023.110714.Peer-Reviewed Original ResearchColon cancer cellsCellular stress response pathwaysStress response pathwaysMulti-omics analysisCancer cellsSecond messenger signalingMulti-omics profilingNew molecular informationFunctional annotationCellular functionsResponse pathwaysKinase signalingCellular pathwaysColon adenocarcinoma cell lineHuman colon adenocarcinoma cell lineApoptosis signalingEnrichment analysisAldehyde dehydrogenase 1B1Molecular signaturesAdenocarcinoma cell lineMolecular informationSignalingNovel targetProtein expressionCell linesShared genetic architecture of blood eosinophil counts and asthma in UK Biobank
Li B, Wang Y, Wang Z, Li X, Kay S, Chupp G, Zhao H, Gomez J. Shared genetic architecture of blood eosinophil counts and asthma in UK Biobank. ERJ Open Research 2023, 9: 00291-2023. PMID: 37650091, PMCID: PMC10463033, DOI: 10.1183/23120541.00291-2023.Peer-Reviewed Original ResearchGenome-wide association studiesGenetic architectureGenetic correlation analysisUK BiobankGWAS resultsTranscription factorsInterleukin-4 SignalingBlood eosinophil countsAssociation studiesDoctor-diagnosed asthmaSignificant variantsEosinophil countEuropean ancestryTraitsPathwayGenetic linkType 2 immune responsesType 2 inflammationSignalingCritical associationImmune responseHeterogeneous diseaseTAGCSevere asthmaTherapeutic interventionsAn 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 factorAktCellsAcetate controls endothelial-to-mesenchymal transition
Zhu X, Wang Y, Soaita I, Lee H, Bae H, Boutagy N, Bostwick A, Zhang R, Bowman C, Xu Y, Trefely S, Chen Y, Qin L, Sessa W, Tellides G, Jang C, Snyder N, Yu L, Arany Z, Simons M. Acetate controls endothelial-to-mesenchymal transition. Cell Metabolism 2023, 35: 1163-1178.e10. PMID: 37327791, PMCID: PMC10529701, DOI: 10.1016/j.cmet.2023.05.010.Peer-Reviewed Original ResearchConceptsTGF-β signalingChronic vascular diseaseTGF-β receptor ALK5Mesenchymal transitionInduction of EndMTVascular diseaseMolecular basisPositive feedback loopReceptor ALK5Cellular levelSMADs 2Novel targetEndMT inductionMetabolic modulationMetabolic basisFibrotic stateSignalingPotential treatmentEndMTTGFDiseaseActivationInductionACSS2PDK47SK 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 functionMethylationMETTL3RibonucleoproteinPhosphorylationTEFbElongationSignalingCD25 recruits inhibitory phosphatases for feedback control of B-cell receptor signaling
Sun R, Lee J, Robinson M, Kume K, Cosgun K, Chan L, Leveille E, Geng H, Vykunta V, Shy B, Marson A, Meffre E, Müschen M. CD25 recruits inhibitory phosphatases for feedback control of B-cell receptor signaling. The Journal Of Immunology 2023, 210: 154.23-154.23. DOI: 10.4049/jimmunol.210.supp.154.23.Peer-Reviewed Original ResearchAntigen-experienced B cellsB cellsEarly B cell developmentGerminal centersB cell developmentSpontaneous germinal centersCD25 surface expressionAutoreactive B cellsRole of CD25B cell toleranceB-cell receptor signalingB-cell leukemiaB cell receptorAutoantibody productionCD25Cell toleranceGenetic ablationReceptor signalingBCR signalingOncogenic signalingInhibitorySuccessful initiationSignalingNegative selectionAutoimmunityCell cycle controls long-range calcium signaling in the regenerating epidermis
Moore J, Bhaskar D, Gao F, Matte-Martone C, Du S, Lathrop E, Ganesan S, Shao L, Norris R, Sanz N, Annusver K, Kasper M, Cox A, Hendry C, Rieck B, Krishnaswamy S, Greco V. Cell cycle controls long-range calcium signaling in the regenerating epidermis. Journal Of Cell Biology 2023, 222: e202302095. PMID: 37102999, PMCID: PMC10140546, DOI: 10.1083/jcb.202302095.Peer-Reviewed Original ResearchThe histamine H3 receptor modulates dopamine D2 receptor–dependent signaling pathways and mouse behaviors
Xu J, Pittenger C. The histamine H3 receptor modulates dopamine D2 receptor–dependent signaling pathways and mouse behaviors. Journal Of Biological Chemistry 2023, 299: 104583. PMID: 36871761, PMCID: PMC10139999, DOI: 10.1016/j.jbc.2023.104583.Peer-Reviewed Original ResearchConceptsStress-activated protein kinase 1Receptor-dependent signaling pathwaysSerine/threonineGlycogen synthase kinase 3 betaSynthase kinase 3 betaProtein kinase 1Phosphorylation of mitogenBiochemical approachesMolecular mechanismsKinase 1Signaling pathwaysProximity ligationBeta signalingBiochemical levelPhosphorylation levelsReceptorsActivationHistamine H3 receptorsPhosphorylationSignalingThreonineAktSpiny projection neuronsD2R functionBetter understandingActivity‐based Tools for Interrogating Host Biology During Infection
Ramanathan R, Hatzios S. Activity‐based Tools for Interrogating Host Biology During Infection. Israel Journal Of Chemistry 2023, 63 PMID: 37744997, PMCID: PMC10512441, DOI: 10.1002/ijch.202200095.Peer-Reviewed Original ResearchActivity-based protein profilingPost-translational modificationsHost post-translational modificationsHost-microbe interactionsHost biologyCells senseCell signalingMicrobial mechanismsEnzyme functionProtein profilingProtein structureSide-chain reactivityChemical probesInfected cellsHost-directed therapiesPotential targetRapid modulationHost responseSignalingBiologyInfectionEnzymeProfilingPathwayPathogensMitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?
Shillingford S, Bennett A. Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable? The Annual Review Of Pharmacology And Toxicology 2023, 63: 617-636. PMID: 36662585, PMCID: PMC10127142, DOI: 10.1146/annurev-pharmtox-051921-121923.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseSmall molecule inhibitionProtein kinaseCritical cellular functionsInhibition of PTPsProtein tyrosineCellular functionsProtein substratesPhosphorylated proteinsCell signalingTyrosine residuesAttractive therapeutic targetCellular effectsKinaseNumerous diseasesPTPDiscovery toolTherapeutic developmentTherapeutic targetMetabolic diseasesInhibitionDephosphorylationSignalingMKPProtein
2022
ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner
Xu X, Chan A, Li M, Liu Q, Mattson N, Pokharel S, Chang W, Yuan Y, Wang J, Moore R, Pirrotte P, Wu J, Su R, Müschen M, Rosen S, Chen J, Yang L, Chen C. ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner. Science Advances 2022, 8: eadc8911. PMID: 36563143, PMCID: PMC9788768, DOI: 10.1126/sciadv.adc8911.Peer-Reviewed Original ResearchCell cycle signalingCRISPR interference screenCell cycle machineryHallmark of tumorigenesisINO80 chromatinInterference screenEpigenetic regulatorsTumor progressionEpigenetic mechanismsCycle machineryEpigenetic dysregulationComplex membersTumor suppressorCell cycleCRISPR geneHCC tumor growthIes6CDKN2A expressionPharmacological inhibitionSignalingMultiple cancersHCC proliferationNovel opportunitiesTumor growthDynamic interplayComprehensive visualization of cell–cell interactions in single-cell and spatial transcriptomics with NICHES
Raredon M, Yang J, Kothapalli N, Lewis W, Kaminski N, Niklason L, Kluger Y. Comprehensive visualization of cell–cell interactions in single-cell and spatial transcriptomics with NICHES. Bioinformatics 2022, 39: btac775. PMID: 36458905, PMCID: PMC9825783, DOI: 10.1093/bioinformatics/btac775.Peer-Reviewed Original ResearchConceptsCell-cell interactionsCell-cell signalingSingle-cell resolutionSingle-cell dataLocal cellular microenvironmentSingle-cell levelSpatial transcriptomics dataCell clustersExtracellular signalingTranscriptomic dataGene expression valuesSpatial transcriptomicsSignaling mechanismCellular microenvironmentNicheExpression valuesSupplementary dataSignalingTranscriptomicsComprehensive visualizationBioinformaticsInteractionA multi-purpose, regenerable, proteome-scale, human phosphoserine resource for phosphoproteomics
Gassaway BM, Li J, Rad R, Mintseris J, Mohler K, Levy T, Aguiar M, Beausoleil SA, Paulo JA, Rinehart J, Huttlin EL, Gygi SP. A multi-purpose, regenerable, proteome-scale, human phosphoserine resource for phosphoproteomics. Nature Methods 2022, 19: 1371-1375. PMID: 36280721, PMCID: PMC9847208, DOI: 10.1038/s41592-022-01638-5.Peer-Reviewed Original ResearchConceptsPhosphorylation site localizationPhosphorylation positionsCellular signalingPosition of phosphorylationProtein phosphorylationComplex biological systemsPhosphorylated isomersData analysis pipelinePhosphoproteomicsAnalysis pipelinePhosphopeptide standardsPhosphorylationPhosphopeptidesCentral roleBiological systemsWeb toolLocalizationSignalingFragmentation spectraN‐Acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling
Cho W, York AG, Wang R, Wyche TP, Piizzi G, Flavell RA, Crawford JM. N‐Acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling. ChemBioChem 2022, 23: e202200490-e202200490. PMID: 36112057, PMCID: PMC9762135, DOI: 10.1002/cbic.202200490.Peer-Reviewed Original ResearchConceptsN-acyl amidesGram-negative opportunistic pathogenNeisseria meningitidisHuman-associated bacteriaBlood-brain barrierBioactive small moleculesInterleukin-10 signalingMacrophage cell typesN-acyltransferaseInterleukin-17AG proteinsHuman diseasesT cellsReceptor signalingCell typesImmune systemHigh mortalityHuman microbiotaRepresentative membersOpportunistic pathogenMeningitidisSignalingSmall moleculesN.MeningitisIsoform-specific inhibition of FGFR signaling achieved by a de-novo-designed mini-protein
Park JS, Choi J, Cao L, Mohanty J, Suzuki Y, Park A, Baker D, Schlessinger J, Lee S. Isoform-specific inhibition of FGFR signaling achieved by a de-novo-designed mini-protein. Cell Reports 2022, 41: 111545. PMID: 36288716, PMCID: PMC9636537, DOI: 10.1016/j.celrep.2022.111545.Peer-Reviewed Original ResearchConceptsFibroblast growth factor receptorC isoformsFibroblast growth factor ligandsLigand-binding regionSilico design strategyIsoform-specific inhibitionGrowth factor ligandsAlternative splicingCellular signalingRegulated processGrowth factor receptorDevelopment of therapeuticsFGFR isoformsFactor ligandCellular analysisFactor receptorMechanistic insightsKlotho proteinSpecific interactionsMB7Distinct subsetsHigh affinitySplicingSignalingFGFOrganization, dynamics and mechanoregulation of integrin-mediated cell–ECM adhesions
Kanchanawong P, Calderwood DA. Organization, dynamics and mechanoregulation of integrin-mediated cell–ECM adhesions. Nature Reviews Molecular Cell Biology 2022, 24: 142-161. PMID: 36168065, PMCID: PMC9892292, DOI: 10.1038/s41580-022-00531-5.Peer-Reviewed Original ResearchConceptsExtracellular matrixCell-ECM adhesionCell-ECM interactionsLocal extracellular matrixAdhesion maturationAdhesion complexesAnimal cellsBiochemical signalingTransmembrane receptorsAdhesion structuresCell shapeIntegrin familyMolecular natureAge-related dysfunctionAdvanced imaging approachesCharacterization of rearrangementsMechanical forcesSignalingTissue formationAdhesionCytoskeletonMechanoregulationImmune responseImaging approachImproved understandingThe noncanonical inflammasome in health and disease
Cahoon J, Yang D, Wang P. The noncanonical inflammasome in health and disease. Infectious Medicine 2022, 1: 208-216. PMID: 38077630, PMCID: PMC10699704, DOI: 10.1016/j.imj.2022.09.001.Peer-Reviewed Original ResearchNoncanonical inflammasomeRapid cellular responsesKey cellular regulatorsInnate immune signalingMechanism of activationAdaptor proteinCellular regulatorsPattern recognition receptorsNon-canonical inflammasomeImmune signalingCaspase-4Cellular responsesRecognition receptorsSubsequent maturationNegative bacterial infectionsCaspase-1Inflammatory cytokinesInflammatory diseasesInflammasomeBacterial infectionsRecent advancesDiseaseSignalingRegulatorProteinPRMT4-mediated arginine methylation promotes tyrosine phosphorylation of VEGFR-2 and regulates filopodia protrusions
Hartsough E, Shelke R, Amraei R, Aryan Z, Lotfollahzadeh S, Rahimi N. PRMT4-mediated arginine methylation promotes tyrosine phosphorylation of VEGFR-2 and regulates filopodia protrusions. IScience 2022, 25: 104736. PMID: 35942094, PMCID: PMC9356023, DOI: 10.1016/j.isci.2022.104736.Peer-Reviewed Original ResearchSrc homology domain 2Protein arginine methyltransferase 4N-terminal domain bindsFilopodia protrusionsVEGFR-2Arginine methylationDomain bindsVascular endothelial growth factor receptor 2 activationSignal transductionTyrosine phosphorylationC-SrcMolecular mechanismsDomain 2MethylationPhosphorylationAngiogenic signalingPathological angiogenesisReceptor 2 activationAngiogenic responseTumor angiogenesisVEGFR-2 inhibitorsEVH1AngiogenesisTransductionSignaling130. De Novo Mutations in 555 Trios Implicate Chromatin Modification, Transcriptional Regulation, and Retinoic Acid Signaling in Syndromic Craniosynostosis
Timberlake A, Allington G, Kiziltug E, Wolfe E, Persing J, Lifton R, Dx G, Kahle K. 130. De Novo Mutations in 555 Trios Implicate Chromatin Modification, Transcriptional Regulation, and Retinoic Acid Signaling in Syndromic Craniosynostosis. Plastic & Reconstructive Surgery Global Open 2022, 10: 85-85. DOI: 10.1097/01.gox.0000842836.76362.eb.Peer-Reviewed Original Research
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