2024
RBX1-CRLs Promote Perinatal Heart Development by Regulating Hippo-YAP Signaling
Zambrano-Carrasco J, Wang W, Ayala J, Sibley J, Carruth J, Jiao K, Li J, Su H. RBX1-CRLs Promote Perinatal Heart Development by Regulating Hippo-YAP Signaling. Physiology 2024, 39: 963. DOI: 10.1152/physiol.2024.39.s1.963.Peer-Reviewed Original ResearchCullin-RING E3 ubiquitin ligasesCongenital heart diseaseCardiomyocyte proliferationCardiac developmentNuclear translocation of YAPTransfer of ubiquitinMulti-subunit complexesE3 ubiquitin ligasePerinatal heart developmentTranslocation of YAPHippo-YAP signalingInactivation of YAPImpaired nuclear translocationCo-transcription factorCardiac malformationsMyocardial hypoplasiaPeripheral edemaAdaptor proteinCKO heartsCullin-RINGLittermate controlsProtein substratesEdU incorporation assayHippo kinasesProtein homeostasis
2023
P-001 ClpX is required in maintaining mitochondrial functions during meiosis and spermatogenesis
Guo C, Xiao Y, Gu J, Hua R, Hai Z, Su J, Wang T. P-001 ClpX is required in maintaining mitochondrial functions during meiosis and spermatogenesis. Human Reproduction 2023, 38 DOI: 10.1093/humrep/dead093.371.Peer-Reviewed Original ResearchGerm cellsMitochondrial functionEnergy of ATP bindingQuality control proteasesHigh-throughput sequencing techniquesApoptotic germ cellsMale germ cellsMeiotic germ cellsCross-over eventsRapamycin treatment in vivoGerm cells of male miceIsolated spermatocytesAAA+ proteasesControl proteasesDegradation tagSpermatogonia differentiationRegulate spermatogenesisCre-loxP systemKnockout mouse lineChromosome synapsisMisfolded proteinsProtein substratesMitochondrial matrixClpXDecreased testicular sizeTeaching an old dog new tricks: A new tool for protein tyrosine phosphatase substrate discovery
Bennett A. Teaching an old dog new tricks: A new tool for protein tyrosine phosphatase substrate discovery. Journal Of Biological Chemistry 2023, 299: 104731. PMID: 37080392, PMCID: PMC10193000, DOI: 10.1016/j.jbc.2023.104731.Peer-Reviewed Original ResearchConceptsIdentification of substratesSubstrate discoveryProtein tyrosineProtein substratesInteraction networksBreast cancer cell modelsCancer cell modelsFunctional interactionNovel targetVersatile new toolNew toolCell modelComplete understandingRecent studiesOld dog new tricksNew tricksInteractorsPTP1B.PTP1BPTPMutationsSubstrateEnzymeTyrosinePathwayProteasomes: Isolation and Activity Assays
Li Y, Tomko R, Hochstrasser M. Proteasomes: Isolation and Activity Assays. Current Protocols 2023, 3: e717. PMID: 37026813, PMCID: PMC10337785, DOI: 10.1002/cpz1.717.Peer-Reviewed Original ResearchConceptsRegulatory particleOne-step purification schemeCore particlesMultisubunit protease complexUbiquitin-proteasome systemUbiquitin polypeptidesUnneeded proteinsYeast SaccharomycesProtein substratesProtease complexProteasomeGel filtration stepPurification schemeProteolytic activityEukaryotesSaccharomycesPolypeptideProteinSubstrateAssaysComplexesMitogen-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 diseasesInhibitionDephosphorylationSignalingMKPProteinBump-and-hole engineering of human polypeptide N-acetylgalactosamine transferases to dissect their protein substrates and glycosylation sites in cells
Calle B, Gonzalez-Rodriguez E, Mahoney K, Cioce A, Bineva-Todd G, Tastan O, Roustan C, Flynn H, Malaker S, Schumann B. Bump-and-hole engineering of human polypeptide N-acetylgalactosamine transferases to dissect their protein substrates and glycosylation sites in cells. STAR Protocols 2023, 4: 101974. PMID: 36633947, PMCID: PMC9843269, DOI: 10.1016/j.xpro.2022.101974.Peer-Reviewed Original ResearchConceptsProtein substratesGlycosylation sitesGalNAc-T familyTransfection of cellsIndividual glycosyltransferasesBioorthogonal reportersN-acetylgalactosamine transferaseSubstrate specificityBiological functionsGalNAc-TsDisease relevanceMolecular biologyComplete detailsGlycosyltransferasesTransferaseCellsBiosynthesisBiologyReporterTransfectionGlycansSubstrateEnzymeHole engineeringSites
2022
The P300 acetyltransferase inhibitor C646 promotes membrane translocation of insulin receptor protein substrate and interaction with the insulin receptor
Peng J, Ramatchandirin B, Wang Y, Pearah A, Namachivayam K, Wolf R, Steele K, MohanKumar K, Yu L, Guo S, White M, Maheshwari A, He L. The P300 acetyltransferase inhibitor C646 promotes membrane translocation of insulin receptor protein substrate and interaction with the insulin receptor. Journal Of Biological Chemistry 2022, 298: 101621. PMID: 35074429, PMCID: PMC8850660, DOI: 10.1016/j.jbc.2022.101621.Peer-Reviewed Original ResearchConceptsAbsence of insulinP300 acetyltransferase activityTyrosine kinase activityAcetyltransferase activityInsulin receptorObese patientsTyrosine phosphorylationRole of acetylationInsulinNormal functionMembrane translocationSubsequent activationC646PatientsLiver hepatocytesProtein substratesInhibitionReceptorsMolecular mechanismsHepatocytesPhosphorylationBeta subunitKinase activityObesityUnique effects
2021
Modulation of Phosphoprotein Activity by Phosphorylation Targeting Chimeras (PhosTACs)
Chen PH, Hu Z, An E, Okeke I, Zheng S, Luo X, Gong A, Jaime-Figueroa S, Crews CM. Modulation of Phosphoprotein Activity by Phosphorylation Targeting Chimeras (PhosTACs). ACS Chemical Biology 2021, 16: 2808-2815. PMID: 34780684, PMCID: PMC10437008, DOI: 10.1021/acschembio.1c00693.Peer-Reviewed Original ResearchConceptsSer/Thr phosphataseChemical biology approachPP2A holoenzymeProtein dephosphorylationBiology approachProtein substratesTranscriptional activationProtein phosphorylationCatalytic subunitCell biologyReporter geneProtein activityRetinoblastoma proteinOff-target effectsCritical proteinsDephosphorylationTernary complexPhosphorylationKinase inhibitorsFOXO3aPROTACsProteinChimerasPhosphataseDrug resistance
2020
Structures of the β‐barrel assembly machine recognizing outer membrane protein substrates
Xiao L, Han L, Li B, Zhang M, Zhou H, Luo Q, Zhang X, Huang Y. Structures of the β‐barrel assembly machine recognizing outer membrane protein substrates. The FASEB Journal 2020, 35: e21207. PMID: 33368572, DOI: 10.1096/fj.202001443rr.Peer-Reviewed Original ResearchConceptsBAM complexFirst β-strandOMP substratesΒ-strandsΒ-barrel outer membrane proteinsΒ-barrel assembly machinery (BAM) complexΒ-barrel assembly machineAssembly machinery complexBamA β-barrelChaperone-bound stateMembrane protein substratesRelated functional analysisLast β-strandFundamental biological processesOuter membrane proteinsDifferent conformational statesOMP biogenesisNutrition acquisitionGram-negative bacteriaProtein substratesMembrane proteinsΒ-barrelFunctional analysisBiological processesConformational states
2018
Flipping ATP to AMPlify Kinase Functions
Sheetz JB, Lemmon MA. Flipping ATP to AMPlify Kinase Functions. Cell 2018, 175: 641-642. PMID: 30340038, PMCID: PMC6421561, DOI: 10.1016/j.cell.2018.10.011.Peer-Reviewed Original ResearchTargeted protein unfolding uncovers a Golgi-specific transcriptional stress response
Serebrenik YV, Hellerschmied D, Toure M, López-Giráldez F, Brookner D, Crews CM. Targeted protein unfolding uncovers a Golgi-specific transcriptional stress response. Molecular Biology Of The Cell 2018, 29: 1284-1298. PMID: 29851555, PMCID: PMC5994893, DOI: 10.1091/mbc.e17-11-0693.Peer-Reviewed Original ResearchConceptsStress responseTranscriptional stress responseChemical biology strategyStress response mechanismsGolgi structural integrityRNA sequence profilesUncharacterized genesEssential organellesEukaryotic cellsCellular homeostasisMisfolded proteinsGolgi targetingTranscriptional responseProtein substratesOrganelle structureProtein modificationHomeostasis mechanismsGolgi apparatusSecretory systemTargeted proteinsProtein unfoldingFurther revealsMajor siteProteinPrecise processing
2017
Protein O-GlcNAcylation: emerging mechanisms and functions
Yang X, Qian K. Protein O-GlcNAcylation: emerging mechanisms and functions. Nature Reviews Molecular Cell Biology 2017, 18: 452-465. PMID: 28488703, PMCID: PMC5667541, DOI: 10.1038/nrm.2017.22.Peer-Reviewed Original ResearchConceptsPost-translational modificationsO-GlcNAcylationAdaptor proteinGlcNAcylation levelsO-GlcNAc homeostasisTetratricopeptide repeat domainDiverse cellular processesProtein-protein interactionsOptimal cellular functionContext-dependent recruitmentPost-translational levelCell signaling dynamicsUnwanted protein aggregationCellular O-GlcNAcylationSubstrate-specific interactionsSpecific cell typesN-acetylglucosamine moietiesLevels of OGTGlcNAc signalingMitochondrial proteinsSpatiotemporal regulationCellular functionsCellular processesEpigenetic modificationsProtein substrates
2015
Actin Cytoskeletal Organization in Drosophila Germline Ring Canals Depends on Kelch Function in a Cullin-RING E3 Ligase
Hudson AM, Mannix KM, Cooley L. Actin Cytoskeletal Organization in Drosophila Germline Ring Canals Depends on Kelch Function in a Cullin-RING E3 Ligase. Genetics 2015, 201: 1117-1131. PMID: 26384358, PMCID: PMC4649639, DOI: 10.1534/genetics.115.181289.Peer-Reviewed Original ResearchConceptsKelch functionE3 ligaseCullin-RING E3 ligaseGermline ring canalsActin cytoskeletal organizationDrosophila kelch proteinUbiquitin ligase activityCross-link F-actinUbiquitin E3 ligaseRing canalsKelch proteinProtein substratesCytoskeletal defectsCytoskeletal organizationCytoskeletal remodelingLigase activityCullin 3KelchF-actinCytoskeletonLigaseProteasomeVivoCul3MutagenesisFormation of Giant Unilamellar Proteo-Liposomes by Osmotic Shock
Motta I, Gohlke A, Adrien V, Li F, Gardavot H, Rothman JE, Pincet F. Formation of Giant Unilamellar Proteo-Liposomes by Osmotic Shock. Langmuir 2015, 31: 7091-7099. PMID: 26038815, PMCID: PMC4950989, DOI: 10.1021/acs.langmuir.5b01173.Peer-Reviewed Original ResearchConceptsGiant unilamellar vesiclesLipid-anchored proteinsOsmotic shockTrans-membrane proteinsSingle giant unilamellar vesiclesProtein substratesPeripheral proteinsSpecific lipidsDifferent proteinsPhotobleaching experimentsFluorescence recoveryCell membraneProteinLarge vesiclesPhysiological conditionsModel systemUnilamellar vesiclesPhospholipid bilayersVesiclesSimple generic methodPrevious dataMembraneHigh concentrationsLipidsBilayersReconstitution of the human U snRNP assembly machinery reveals stepwise Sm protein organization
Neuenkirchen N, Englbrecht C, Ohmer J, Ziegenhals T, Chari A, Fischer U. Reconstitution of the human U snRNP assembly machinery reveals stepwise Sm protein organization. The EMBO Journal 2015, 34: 1925-1941. PMID: 26069323, PMCID: PMC4547896, DOI: 10.15252/embj.201490350.Peer-Reviewed Original ResearchConceptsSMN complexAssembly machinerySm proteinsSpliceosomal U snRNPsDetailed molecular dissectionTrans-acting factorsSpontaneous conformational changesBiochemical reconstitutionPRMT5 complexU snRNPsProtein complexesMolecular dissectionProtein substratesProtein organizationIndividual proteinsConformational changesFaithful deliveryMode of actionRecombinant sourcesCoordinated actionBrownian machineMechanistic insightsSnRNPsProteinAssembly reaction
2012
Cyclic GMP-dependent Stimulation of Serotonin Transport Does Not Involve Direct Transporter Phosphorylation by cGMP-dependent Protein Kinase*
Wong A, Zhang YW, Jeschke GR, Turk BE, Rudnick G. Cyclic GMP-dependent Stimulation of Serotonin Transport Does Not Involve Direct Transporter Phosphorylation by cGMP-dependent Protein Kinase*. Journal Of Biological Chemistry 2012, 287: 36051-36058. PMID: 22942288, PMCID: PMC3476273, DOI: 10.1074/jbc.m112.394726.Peer-Reviewed Original ResearchConceptsCGMP-dependent protein kinaseProtein kinaseATP analogUnidentified protein kinasesWild-type kinaseMitogen-activated protein kinaseP38 mitogen-activated protein kinasePhosphorylation site sequencePKG-dependent phosphorylationModel peptide substratesTransporter phosphorylationKinase cascadePhosphorylation sitesWT kinaseDirect substrateProtein substratesResidue mutantsSerotonin transporterPeptide library screeningSite sequenceP38 inhibitorLibrary screeningKinasePeptide substratesCultured cells
2010
Deciphering Protein Kinase Specificity Through Large-Scale Analysis of Yeast Phosphorylation Site Motifs
Mok J, Kim PM, Lam HY, Piccirillo S, Zhou X, Jeschke GR, Sheridan DL, Parker SA, Desai V, Jwa M, Cameroni E, Niu H, Good M, Remenyi A, Nianhan J, Sheu YJ, Sassi HE, Sopko R, Chan CS, De Virgilio C, Hollingsworth NM, Lim WA, Stern DF, Stillman B, Andrews BJ, Gerstein MB, Snyder M, Turk BE. Deciphering Protein Kinase Specificity Through Large-Scale Analysis of Yeast Phosphorylation Site Motifs. Science Signaling 2010, 3: ra12. PMID: 20159853, PMCID: PMC2846625, DOI: 10.1126/scisignal.2000482.Peer-Reviewed Original ResearchConceptsPhosphorylation site motifsSite motifShort linear sequence motifsKinase substrate recognitionKinase-substrate relationshipsProtein kinase specificityKinase catalytic domainLinear sequence motifsPrediction of thousandsCMGC groupKinase specificityPhosphorylation targetsKinase substrateYeast proteomeSequence motifsSubstrate recognitionKinase familyProtein substratesCatalytic domainProtein kinaseLarge-scale analysisPrimary sequenceCandidate substratesComputational scanningKinase
2008
Defective signal transduction in B lymphocytes lacking presenilin proteins
Yagi T, Giallourakis C, Mohanty S, Scheidig C, Shen J, Zheng H, Xavier RJ, Shaw AC. Defective signal transduction in B lymphocytes lacking presenilin proteins. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 979-984. PMID: 18195359, PMCID: PMC2242696, DOI: 10.1073/pnas.0707755105.Peer-Reviewed Original ResearchConceptsPresenilin proteinsDiverse cellular processesMultiple genomic datasetsPS proteinsSignal transduction eventsWhole-genome datasetsDefective signal transductionNotch family membersCalcium-dependent signalingCellular processesProtein substratesSignal transductionTransduction eventsProtein interactionsPS2 functionUnanticipated roleConditional alleleGenomic datasetsToll-like receptor signalingPathway analysisIntegrative analysisPosttranslational cleavageReceptor signalingRecombinase expressionProtein
2007
Dissecting kinase signaling pathways
Boyle SN, Koleske AJ. Dissecting kinase signaling pathways. Drug Discovery Today 2007, 12: 717-724. PMID: 17826684, DOI: 10.1016/j.drudis.2007.07.019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBenzamidesDrug Delivery SystemsHumansImatinib MesylateLapatinibNeoplasmsPhosphoproteinsPhosphorylationPiperazinesProtein Kinase InhibitorsProtein KinasesProteomicsPyrimidinesQuinazolinesSignal TransductionTrastuzumabConceptsSame protein substrateProtein Kinase SignalingKinase substratePutative substratesProtein substratesKinase signalingProtein kinaseMultiple kinasesPhysiological substratesKinaseHuman diseasesDrug targetsPhysiological relevanceSubstrate interactionsKinase inhibitorsPathwaySignalingSubstrateNeurological disordersInteractionHallmarkInhibitorsTarget
2002
Combinatorial Strategies for Targeting Protein Families: Application to the Proteases
Maly DJ, Huang L, Ellman JA. Combinatorial Strategies for Targeting Protein Families: Application to the Proteases. ChemBioChem 2002, 3: 16-37. PMID: 17590950, DOI: 10.1002/1439-7633(20020104)3:1<16::aid-cbic16>3.0.co;2-z.Peer-Reviewed Original ResearchConceptsProtein familySmall molecule inhibitorsCombinatorial librariesPhysiological protein substratesCell-permeable small-molecule inhibitorsSubstrate specificity profilePowerful chemical toolsInhibitor design effortsCombinatorial chemistryProteomics effortsUbiquitous familyProtein substratesChemical toolsProtease functionNew proteinsSequence homologySmall moleculesNumerous proteasesCommon scaffoldSystematic studySpecificity informationProteinProteaseRecent large scaleMechanistic characteristics
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