2025
Epigenetic regulation of cancer stemness
Galassi C, Manic G, Esteller M, Galluzzi L, Vitale I. Epigenetic regulation of cancer stemness. Signal Transduction And Targeted Therapy 2025, 10: 243. PMID: 40744921, PMCID: PMC12314033, DOI: 10.1038/s41392-025-02340-6.Peer-Reviewed Original ResearchConceptsEpigenetic controlEpigenetic control of transcriptionReversible modificationsControl of transcriptionImpact of epigenetic alterationsModification of DNAEpigenetic marksDeubiquitinating enzymesUbiquitin ligasePreservation of homeostasisTranscription factorsEpigenetic defectsPostembryonic developmentEpigenetic alterationsEpigenetic modifiersRegulation of cancer stemnessGene expressionAdult tissuesHuman disordersActivation statusCancer stem cellsCancer stemnessAntagonistic activitySmall populationMalignant cells
2024
TET3-overexpressing macrophages promote endometriosis
Lv H, Liu B, Dai Y, Li F, Bellone S, Zhou Y, Mamillapalli R, Zhao D, Venkatachalapathy M, Hu Y, Carmichael G, Li D, Taylor H, Huang Y. TET3-overexpressing macrophages promote endometriosis. Journal Of Clinical Investigation 2024, 134: e181839. PMID: 39141428, PMCID: PMC11527447, DOI: 10.1172/jci181839.Peer-Reviewed Original ResearchDisease-associated macrophagesTET3 overexpressionHuman endometriosis lesionsPathophysiology of endometriosisPro-inflammatory cytokine productionChronic inflammatory diseaseReproductive age womenEndometriosis lesionsE3 ubiquitin ligasePathogenic macrophagesCytokine productionEndometriosisInflammatory diseasesTET3 knockdownEndometriosis progressionPathogenic contributorsLet-7 miRNA expressionAge womenMacrophagesMouse macrophagesTherapeutic targetUbiquitin ligaseTET3MiceDiseaseA circadian clock output functions independently of phyB to sustain daytime PIF3 degradation
Liu W, Lowrey H, Xu A, Leung C, Adamchek C, He J, Du J, Chen M, Gendron J. A circadian clock output functions independently of phyB to sustain daytime PIF3 degradation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2408322121. PMID: 39163340, PMCID: PMC11363348, DOI: 10.1073/pnas.2408322121.Peer-Reviewed Original ResearchConceptsPhytochrome-interacting factorsF-boxRed-light photoreceptor phytochrome BPhotoreceptor phytochrome BCircadian clock outputE3 ubiquitin ligaseDownstream biological processesPhyB signalingGrowth-regulating mechanismsTranscriptional connectionsPhytochrome BClock's roleRhythmic transcriptionUbiquitin ligaseClock regulationGenetic evidenceMonochromatic red lightProtein stabilityCircadian clockPhyBBiological processesPlant growthClock outputCircadian expressionRegulation mechanismUBXN3B is crucial for B lymphopoiesis
Geng T, Yang D, Lin T, Harrison A, Wang B, Cao Z, Torrance B, Fan Z, Wang K, Wang Y, Yang L, Haynes L, Cheng G, Vella A, Flavell R, Pereira J, Fikrig E, Wang P. UBXN3B is crucial for B lymphopoiesis. EBioMedicine 2024, 106: 105248. PMID: 39018756, PMCID: PMC11287013, DOI: 10.1016/j.ebiom.2024.105248.Peer-Reviewed Original ResearchUbiquitin regulatory XPre-BCR signalingB cell receptorB lymphopoiesisKnockout miceValosin-containing proteinCaspase-3 protein levelsCell cycle arrestBone marrow transferNormal B lymphopoiesisUbiquitin ligaseIncreased viral loadCell-intrinsic mannerPathogenesis of severe acute respiratory syndrome coronavirus 2RNA sequencingCycle arrestDNA virusesCell survivalMarrow transferMultiple virusesSingle-cellImmunofluorescence microscopyViral loadMature BRespiratory virusesHyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis
Wen P, Lei H, Deng H, Deng S, Tirado C, Wang M, Mu P, Zheng Y, Pan D. Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis. Genes & Development 2024, 38: 675-691. PMID: 39137945, PMCID: PMC11368183, DOI: 10.1101/gad.351856.124.Peer-Reviewed Original ResearchConceptsPolycomb Repressive Complex1Tumor suppressor pathwayTissue growth controlSuppressor pathwayProtein degradationZinc finger genesGrowth controlUbiquitin-mediated degradationE3 ubiquitin ligasePolycomb repressive complexesProtein degradation pathwaysTumor suppressor geneHyperplastic discsFinger genesMammalian homologSubstrate adaptorRepressive complexesUbiquitin ligaseEmbryonic segmentationProtein complexesModel organismsHuman geneticsUpstream regulatorSuppressor geneProstate cancer tumorigenesisStructural insights into PPP2R5A degradation by HIV-1 Vif
Hu Y, Delviks-Frankenberry K, Wu C, Arizaga F, Pathak V, Xiong Y. Structural insights into PPP2R5A degradation by HIV-1 Vif. Nature Structural & Molecular Biology 2024, 31: 1492-1501. PMID: 38789685, PMCID: PMC12221852, DOI: 10.1038/s41594-024-01314-6.Peer-Reviewed Original ResearchHost-virus protein interactionsCullin RING E3 ubiquitin ligasesInduced G2/M cell cycle arrestSets of proteinsG2/M cell cycle arrestSubstrate-binding siteCryogenic-electron microscopy structuresProtein phosphatase 2ADegradation-independent mechanismCell cycle arrestUbiquitin ligaseProtein interactionsPhosphatase 2AAntiviral proteinCycle arrestDegradation-dependentA-resolutionHIV-1 VifPPP2R5AStructural insightsDiverse interactionsProteinCellular studiesPhosphatase activityPotential targetEmerging Roles of Cullin-RING Ubiquitin Ligases in Cardiac Development
Zambrano-Carrasco J, Zou J, Wang W, Sun X, Li J, Su H. Emerging Roles of Cullin-RING Ubiquitin Ligases in Cardiac Development. Cells 2024, 13: 235. PMID: 38334627, PMCID: PMC10854628, DOI: 10.3390/cells13030235.Peer-Reviewed Original ResearchConceptsUbiquitin ligaseFamily of ubiquitin ligasesCullin-RING ubiquitin ligasesE3 ubiquitin ligaseRegulation of heart developmentPost-translational mechanismsHeart developmentRegulation of cardiac morphogenesisCongenital heart diseaseCardiac developmental processesSpatiotemporally regulated processCullin-RINGDevelopment of innovative therapiesEpigenetic regulationIntracellular proteinsLigaseMolecular mechanismsDevelopmental processesHeart failureInnovative therapiesCardiac developmentCardiac morphogenesisPostnatal stagesHeart diseaseOrchestrated process
2023
Atorvastatin rescues vascular endothelial injury in hypertension by WWP2-mediated ubiquitination and degradation of ATP5A
Yin Z, You S, Zhang S, Zhang L, Wu B, Huang X, Lu S, Cao L, Zhang Y, Li D, Zhang X, Liu J, Sun Y, Zhang N. Atorvastatin rescues vascular endothelial injury in hypertension by WWP2-mediated ubiquitination and degradation of ATP5A. Biomedicine & Pharmacotherapy 2023, 166: 115228. PMID: 37557013, DOI: 10.1016/j.biopha.2023.115228.Peer-Reviewed Original ResearchConceptsMitochondrial pathway of apoptosisRegulate protein ubiquitinationPathway of apoptosisE3 ubiquitin ligaseVascular endothelial injuryDeath of vascular endothelial cellsEndothelial injuryMitochondrial pathwayUbiquitin ligaseWWP2 overexpressionProteasome pathwayProtein ubiquitinationBcl-2/BaxBiological processesWWP2Vascular endotheliumATP5ALipid-lowering drugsUbiquitinEffect of atorvastatinImproving vascular endothelial functionVascular endothelial functionDamaged vascular endotheliumVascular endothelial cellsMechanism of atorvastatin
2022
PROTACs: past, present and future
Li K, Crews CM. PROTACs: past, present and future. Chemical Society Reviews 2022, 51: 5214-5236. PMID: 35671157, PMCID: PMC10237031, DOI: 10.1039/d2cs00193d.Peer-Reviewed Original ResearchConceptsProtein of interestProteolysis-targeting chimerasUbiquitin-proteasome systemE3 ubiquitin ligaseSmall molecule inhibitorsUbiquitin ligaseNonenzymatic functionProtein degradationHeterobifunctional moleculesDrug resistance mechanismsMolecule inhibitorsSubsequent degradationUbiquitinationLigasePromising therapeuticsProteinChimerasPotential toxicityDegradationMechanism
2021
AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections
Bone N, Becker E, Husain M, Jiang S, Zmijewska A, Park D, Chacko B, Darley-Usmar V, Grégoire M, Tadie J, Thannickal V, Zmijewski J. AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections. Scientific Reports 2021, 11: 12387. PMID: 34117280, PMCID: PMC8196038, DOI: 10.1038/s41598-021-90573-0.Peer-Reviewed Original ResearchConceptsAMPK activationEffects of AMPK activationClearance of dysfunctional mitochondriaSecondary bacterial lung infectionImpact of AMPKParkin ubiquitin ligaseBacterial lung infectionsRecruitment of ParkinImmune defenseResponse to bacterial infectionDepolarization of mitochondriaLevels of ParkinBacterial infectionsHost immune defenseAMPK deficiencyControls mitophagyBioenergetic plasticityKilling of pathogenic bacteriaUbiquitin ligaseDysfunctional mitochondriaImmunosuppressive phenotypeBacterial pathogensLung infectionAMPK levelsWild typeTissue-specific dynamic codon redefinition in Drosophila
Hudson AM, Szabo NL, Loughran G, Wills NM, Atkins JF, Cooley L. Tissue-specific dynamic codon redefinition in Drosophila. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2012793118. PMID: 33500350, PMCID: PMC7865143, DOI: 10.1073/pnas.2012793118.Peer-Reviewed Original ResearchConceptsStop codonTranslational stop codon readthroughReadthrough efficiencyHuman tissue culture cellsStop codon readthroughTissue-specific regulationAdult central nervous system (CNS) tissueTissue culture cellsReadthrough productKelch proteinUbiquitin ligaseSingle geneAdult brainIndividual proteinsCodon readthroughReadthroughViral mRNAsC-terminalMalpighian tubulesCodonNeuronal proteinsCell typesAmino acidsCulture cellsDrosophila
2020
Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex
Wu X, Siggel M, Ovchinnikov S, Mi W, Svetlov V, Nudler E, Liao M, Hummer G, Rapoport TA. Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex. Science 2020, 368 PMID: 32327568, PMCID: PMC7380553, DOI: 10.1126/science.aaz2449.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCryoelectron MicroscopyEndoplasmic ReticulumEndoplasmic Reticulum-Associated DegradationMembrane GlycoproteinsMembrane ProteinsMolecular Dynamics SimulationMultiprotein ComplexesProtein DomainsProtein FoldingProteolysisSaccharomyces cerevisiae ProteinsUbiquitin-Protein LigasesConceptsHrd1 complexLuminal endoplasmic reticulum proteinsCryo-electron microscopy analysisHrd1 ubiquitin ligaseEndoplasmic reticulum proteinER membraneUbiquitin ligaseProtein degradationStructural basisReticulum proteinsPolypeptide loopMembrane regionsLateral gateLuminal binding sitesBinding sitesLuminal cavityForm twoYos9RetrotranslocationERADMicroscopy analysisSubcomplexLigaseHRD1ProteasomeThe Relationship between ER Stress and Protein Quality Control at the Translocon
Broshar C, Buchanan B, Mehrtash A, Runnebohm A, Snow B, Scanameo L, Hochstrasser M, Rubenstein E. The Relationship between ER Stress and Protein Quality Control at the Translocon. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.00497.Peer-Reviewed Original ResearchProtein quality controlUbiquitin-proteasome systemER stressUbiquitin ligaseDegradation signalProtein quality control mechanismsHrd1 ubiquitin ligaseTranslocon-associated proteinLipid homeostasisStress-sensing mechanismsStress-responsive mechanismsQuality control mechanismsDegradation of proteinsERAD pathwayModel organismsEndoplasmic reticulum stressProtein misfoldingAberrant proteinsERADImpairs degradationProtein degradationProteins misfoldHeat shockEndoplasmic reticulumProtein
2017
Infection-derived lipids elicit an immune deficiency circuit in arthropods
Shaw DK, Wang X, Brown LJ, Chávez AS, Reif KE, Smith AA, Scott AJ, McClure EE, Boradia VM, Hammond HL, Sundberg EJ, Snyder GA, Liu L, DePonte K, Villar M, Ueti MW, de la Fuente J, Ernst RK, Pal U, Fikrig E, Pedra JH. Infection-derived lipids elicit an immune deficiency circuit in arthropods. Nature Communications 2017, 8: 14401. PMID: 28195158, PMCID: PMC5316886, DOI: 10.1038/ncomms14401.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnaplasma marginaleAnaplasma phagocytophilumAnimalsArthropodsBorrelia burgdorferiCarrier ProteinsDisease Models, AnimalDrosophila melanogasterDrosophila ProteinsEscherichia coliFas-Associated Death Domain ProteinGene SilencingHEK293 CellsHumansImmunologic Deficiency SyndromesIxodesLipidsLyme DiseasePhosphatidylglycerolsRecombinant ProteinsRNA, Small InterferingSignal TransductionTranscription FactorsUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesX-Linked Inhibitor of Apoptosis ProteinConceptsAdaptor molecule FasImmune deficiency (IMD) pathwayPeptidoglycan recognition proteinsE3 ubiquitin ligaseLyme disease spirochete Borrelia burgdorferiIMD pathwayGram-negative bacteriaRecognition proteinsUbiquitin ligaseDeath domainApoptosis proteinDistinct bacteriaBiochemical interactionsMolecule FasSpirochete Borrelia burgdorferiReceptor networkA. marginaleProteinAnaplasma phagocytophilumBacteriaPathwayBorrelia burgdorferiInsectsLipidsArthropods
2016
Loss of Cbl-PI3K interaction modulates the periosteal response to fracture by enhancing osteogenic commitment and differentiation
Scanlon V, Walia B, Yu J, Hansen M, Drissi H, Maye P, Sanjay A. Loss of Cbl-PI3K interaction modulates the periosteal response to fracture by enhancing osteogenic commitment and differentiation. Bone 2016, 95: 124-135. PMID: 27884787, PMCID: PMC5819877, DOI: 10.1016/j.bone.2016.11.020.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseAnimalsBiomarkersCell CountCell DifferentiationCell LineageCell NucleusCell ProliferationFracture HealingFractures, BoneMesodermMice, Inbred C57BLMutationOsteogenesisPeriosteumPhosphatidylinositol 3-KinasePhosphorylationProtein BindingProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-cblSp7 Transcription FactorUp-RegulationConceptsCbl-PI3K interactionUbiquitin ligase functionMultipotent skeletal progenitorsPeriosteal cellsPI3KMajor adaptor proteinP85 regulatory subunitTranscriptional target genesE3 ubiquitin ligaseOsteogenic differentiationPhosphatidylinositol-3 kinasePI3K regulationMajor signaling proteinsK interactionPI3K activityPeriosteal thickeningLipid kinasesP85 subunitSkeletal progenitorsAdaptor proteinRegulatory subunitLigase functionSignaling proteinsUbiquitin ligaseNuclear localization
2012
The E6AP E3 ubiquitin ligase regulates the cellular response to oxidative stress
Wolyniec K, Levav-Cohen Y, Jiang Y, Haupt S, Haupt Y. The E6AP E3 ubiquitin ligase regulates the cellular response to oxidative stress. Oncogene 2012, 32: 3510-3519. PMID: 22986523, DOI: 10.1038/onc.2012.365.Peer-Reviewed Original ResearchConceptsE3 ubiquitin ligaseReactive oxygen speciesUbiquitin ligaseStress responseCellular responsesE6AP expressionStress conditionsImportant stress conditionsCell growthCellular stress responseAppropriate cellular responsesOxidative stress responseSpecific stress conditionsOxidative stressIntracellular reactive oxygen speciesOncogenic RasCellular senescenceGrowth-suppressive effectsOxidative DNA damageApoptotic responseNovel roleCell deathImportant regulatorE6APDNA damage
2011
E6AP is required for replicative and oncogene-induced senescence in mouse embryo fibroblasts
Levav-Cohen Y, Wolyniec K, Alsheich-Bartok O, Chan A, Woods S, Jiang Y, Haupt S, Haupt Y. E6AP is required for replicative and oncogene-induced senescence in mouse embryo fibroblasts. Oncogene 2011, 31: 2199-2209. PMID: 21927031, DOI: 10.1038/onc.2011.402.Peer-Reviewed Original ResearchConceptsMouse embryo fibroblastsOncogene-induced senescenceCellular responsesEmbryo fibroblastsCellular stress responseRas-induced senescenceE3 ubiquitin ligaseStress-induced accumulationRole of E6APUbiquitin ligaseProtein regulatorsTissue homeostasisReplicative senescenceCellular senescenceCell cycleStress responseImportant regulatorSenescenceStress conditionsE6APIndependent growthEnhanced growthEnhanced proliferationReplicativeRegulator
2009
POSH Stimulates the Ubiquitination and the Clathrin-independent Endocytosis of ROMK1 Channels*
Lin DH, Yue P, Pan CY, Sun P, Zhang X, Han Z, Roos M, Caplan M, Giebisch G, Wang WH. POSH Stimulates the Ubiquitination and the Clathrin-independent Endocytosis of ROMK1 Channels*. Journal Of Biological Chemistry 2009, 284: 29614-29624. PMID: 19710010, PMCID: PMC2785594, DOI: 10.1074/jbc.m109.041582.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBiological TransportCell LineClathrinDynaminsEpithelial Sodium ChannelsGene Expression RegulationHumansKidney Tubules, CollectingOocytesPotassium Channels, Inwardly RectifyingProtein Sorting SignalsProtein Structure, TertiaryRatsRats, Sprague-DawleyUbiquitinationUbiquitin-Protein LigasesXenopus laevisConceptsHEK293T cellsClathrin-independent endocytosisE3 ubiquitin ligaseUbiquitin ligaseGlutathione S-transferase pulldown experimentsROMK1 channelsT cellsTyrosine-based internalization signalPotassium currentROMK channelsDominant-negative dynaminImmunoprecipitation of lysatesInternalization signalInhibitory effectPulldown experimentsScaffold proteinUbiquitination assaysRING domainUbiquitinationN-terminusGamma subunitsAmino acidsENaC-alphaROMK1Tissue lysatesEndothelial and Smooth Muscle-derived Neuropilin-like Protein Regulates Platelet-derived Growth Factor Signaling in Human Vascular Smooth Muscle Cells by Modulating Receptor Ubiquitination*
Guo X, Nie L, Esmailzadeh L, Zhang J, Bender JR, Sadeghi MM. Endothelial and Smooth Muscle-derived Neuropilin-like Protein Regulates Platelet-derived Growth Factor Signaling in Human Vascular Smooth Muscle Cells by Modulating Receptor Ubiquitination*. Journal Of Biological Chemistry 2009, 284: 29376-29382. PMID: 19696027, PMCID: PMC2785569, DOI: 10.1074/jbc.m109.049684.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDown-RegulationHumansMembrane ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Muscle, Smooth, VascularMyocytes, Smooth MusclePhosphorylationPlatelet-Derived Growth FactorProto-Oncogene Proteins c-cblReceptor, Platelet-Derived Growth Factor betaSignal Transductionsrc-Family KinasesUbiquitin-Protein LigasesUbiquitinationConceptsPlatelet-derived growth factorSmooth muscle cell-derived neuropilin-like proteinPDGF receptorPlatelet-derived growth factor signalingPrototypic growth factorsE3 ubiquitin ligaseGrowth factor signalingExpression levelsPrimary human VSMCsHuman vascular smooth muscle cellsVascular smooth muscle cell growthReceptor ubiquitinationGrowth factorUbiquitin ligaseFactor signalingRNA interferenceC-CblVascular smooth muscle cellsSmooth muscle cell growthMuscle cell growthVSMC DNA synthesisUbiquitinationESDNHuman VSMCsSmooth muscle cellsThe E3 ubiquitin ligase specificity subunit ASB2β is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation
Bello NF, Lamsoul I, Heuzé ML, Métais A, Moreaux G, Calderwood DA, Duprez D, Moog-Lutz C, Lutz PG. The E3 ubiquitin ligase specificity subunit ASB2β is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation. Cell Death & Differentiation 2009, 16: 921-932. PMID: 19300455, PMCID: PMC2709956, DOI: 10.1038/cdd.2009.27.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCell DifferentiationCell LineChickensContractile ProteinsFilaminsGene Knockdown TechniquesHumansMiceMicrofilament ProteinsMyoblastsProteasome Endopeptidase ComplexRNA InterferenceRNA, MessengerSuppressor of Cytokine Signaling ProteinsUbiquitin-Protein LigasesConceptsFilamin BMuscle differentiationSpecificity subunitAnkyrin repeat-containing proteinActive E3 ubiquitin ligaseE3 ubiquitin ligase complexRepeat-containing proteinUbiquitin ligase complexE3 ubiquitin ligaseSuppressor of cytokineBox 2 geneLigase complexE3 ubiquitinUbiquitin ligaseProteasomal degradationMyoblast fusionNovel regulatorMuscle developmentKnockdown cellsProtein degradationMyogenic differentiationAdult tissuesC2C12 cellsMuscle contractile proteinsInduced differentiation
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