2023
Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE
Chongsaritsinsuk J, Steigmeyer A, Mahoney K, Rosenfeld M, Lucas T, Smith C, Li A, Ince D, Kearns F, Battison A, Hollenhorst M, Judy Shon D, Tiemeyer K, Attah V, Kwon C, Bertozzi C, Ferracane M, Lemmon M, Amaro R, Malaker S. Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE. Nature Communications 2023, 14: 6169. PMID: 37794035, PMCID: PMC10550946, DOI: 10.1038/s41467-023-41756-y.Peer-Reviewed Original ResearchConceptsFamily of proteinsMucin domainO-glycosylationBiological functionsKey regulatorComplex glycansMass spectrometric analysisFunctional relevanceTIM familyDetailed molecular structureCritical roleGlycosylationProteinSpectrometric analysisStructural featuresUnique abilityStructural dynamicsMolecular dynamics simulationsTim-3 functionFamilyPowerful workflowRegulatorImmune cellsCheckpointGlycans3108 – PHOSPHORYLATION OF RUNX1 PROMOTES MEGAKARYOCYTIC FATE IN MEGAKARYOCYTE-ERYTHROID PROGENITOR FATE SPECIFICATION
Kwon N, Lu Y, Thompson E, Wang L, Zhang P, Krause D. 3108 – PHOSPHORYLATION OF RUNX1 PROMOTES MEGAKARYOCYTIC FATE IN MEGAKARYOCYTE-ERYTHROID PROGENITOR FATE SPECIFICATION. Experimental Hematology 2023, 124: s104. DOI: 10.1016/j.exphem.2023.06.215.Peer-Reviewed Original ResearchMegakaryocyte-erythroid progenitorsFate specificationHEL cellsGene expressionSingle-cell RNA-seq dataPost-translational modificationsDifferential gene expressionRNA-seq dataChromatin localizationRNA-seqPhosphorylation statusRUNX1 overexpressionE progenitorsTranscriptional activityKey regulatorRUNX1 mRNAMK progenitorsT residuesGenesErythroid progenitorsRUNX1MKPProgenitorsProtein levelsSpecification mechanism
2022
MtING2 encodes an ING domain PHD finger protein which affects Medicago growth, flowering, global patterns of H3K4me3, and gene expression
Jaudal M, Mayo‐Smith M, Poulet A, Whibley A, Peng Y, Zhang L, Thomson G, Trimborn L, Jacob Y, van Wolfswinkel J, Goldstone D, Wen J, Mysore K, Putterill J. MtING2 encodes an ING domain PHD finger protein which affects Medicago growth, flowering, global patterns of H3K4me3, and gene expression. The Plant Journal 2022, 112: 1029-1050. PMID: 36178149, PMCID: PMC9828230, DOI: 10.1111/tpj.15994.Peer-Reviewed Original ResearchConceptsGene-edited mutantsGene expressionWinter-annual ArabidopsisWild-type plantsPlant homeodomain (PHD) fingerStrong mutant phenotypePHD finger proteinChIP-seq analysisRNA sequencing experimentsExpression of activatorsPHD fingerMutant phenotypeFinger proteinMedicago truncatulaImportant physiological roleAbnormal leavesInsertion mutantsMutant studiesEpigenetic mechanismsMost plantsSmall seedsGrowth genesKey regulatorWild typeMutantsMetabolic Regulation of Mitochondrial Dynamics and Cardiac Function
Rudokas M, Cacheux M, Akar F. Metabolic Regulation of Mitochondrial Dynamics and Cardiac Function. 2022, 197-211. DOI: 10.1007/978-3-031-08309-9_6.BooksMitochondrial dynamicsNormal embryonic developmentMitochondrial dynamics proteinsDynamic organellesMitochondrial networkMitochondrial fusionDynamic proteinsEmbryonic developmentFragmented mitochondriaKey proteinsKey regulatorFunctional importanceMetabolic regulationAltered regulationMitochondriaFission eventsFundamental processesProteinCardiac mitochondriaFission resultsRegulationMorphological changesRecent advancesOrganellesRegulatorSH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP
Chau JE, Vish KJ, Boggon TJ, Stiegler AL. SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP. Nature Communications 2022, 13: 4788. PMID: 35970859, PMCID: PMC9378701, DOI: 10.1038/s41467-022-32541-4.Peer-Reviewed Original ResearchConceptsRhoGAP activitySH3 domainCatalytic arginine fingerIntrinsic GTPase activityRho family GTPasesLiver cancer 1GAP proteinsRhoGAP proteinArginine fingerCo-crystal structureRas GTPasesGAP activityRho proteinsCellular processesGTPase activityMolecular basisKey regulatorTumor suppressorP120RasGAPCell migrationProteinGTPasesRhoGAPCancer 1Binding sitesA controlled random gene perturbation method identifies ARPC1B gene as a key regulator of cancer metastasis
Chang D, Du H, Chen X, Bian X, Tian W, Shen J, Wei Y, Jiang Y, Dela Cruz C, Xie L, Sharma L, Li K. A controlled random gene perturbation method identifies ARPC1B gene as a key regulator of cancer metastasis. Genes & Diseases 2022, 10: 687-689. PMID: 37396530, PMCID: PMC10308106, DOI: 10.1016/j.gendis.2022.06.006.Peer-Reviewed Original ResearchZebrafish models of Alx-linked frontonasal dysplasia reveal a role for Alx1 and Alx3 in the anterior segment and vasculature of the developing eye
Yoon B, Yeung P, Santistevan N, Bluhm L, Kawasaki K, Kueper J, Dubielzig R, Vanoudenhove J, Cotney J, Liao E, Grinblat Y. Zebrafish models of Alx-linked frontonasal dysplasia reveal a role for Alx1 and Alx3 in the anterior segment and vasculature of the developing eye. Biology Open 2022, 11: bio059189. PMID: 35142342, PMCID: PMC9167625, DOI: 10.1242/bio.059189.Peer-Reviewed Original ResearchConceptsALX geneAnterior neurocraniumZebrafish modelGenetic mechanismsNovel roleAnterior segment formationHomeobox transcription factorCranial neural crestOxidative stress responseParalogous genesConserved roleAnterior segment defectsAbsence of eyesEthanol toxicityTranscription factorsTranscriptomic analysisLineage labelingAlx1Midfacial morphogenesisKey regulatorNeural crestStress responseSegment formationMutantsVascular developmentType I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells
Sumida TS, Dulberg S, Schupp JC, Lincoln MR, Stillwell HA, Axisa PP, Comi M, Unterman A, Kaminski N, Madi A, Kuchroo VK, Hafler DA. Type I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells. Nature Immunology 2022, 23: 632-642. PMID: 35301508, PMCID: PMC8989655, DOI: 10.1038/s41590-022-01152-y.Peer-Reviewed Original ResearchConceptsCoinhibitory receptor expressionHuman T cellsIFN-I responsesCoinhibitory receptorsT cellsTIGIT expressionReceptor expressionAcute SARS-CoV-2 infectionPD-1/TimSARS-CoV-2 infectionEnhancement of immunotherapyType 1 interferonT-cell featuresLAG-3Infectious diseasesDifferent temporal kineticsTranscription factorsCancer therapyReceptorsCell featuresKey transcription factorIFNPresent studyMRNA profilingKey regulatorPrdm6 controls heart development by regulating neural crest cell differentiation and migration
Hong L, Li N, Gasque V, Mehta S, Ye L, Wu Y, Li J, Gewies A, Ruland J, Hirschi KK, Eichmann A, Hendry C, van Dijk D, Mani A. Prdm6 controls heart development by regulating neural crest cell differentiation and migration. JCI Insight 2022, 7: e156046. PMID: 35108221, PMCID: PMC8876496, DOI: 10.1172/jci.insight.156046.Peer-Reviewed Original ResearchConceptsCardiac NCCNeural crest cell fateNeural crest cell differentiationSingle-cell RNA-seq analysisRNA-seq analysisDorsal neural tubeG1-S progressionFate-mapping approachCNCC migrationSpecification genesH4K20 monomethylationCell fateTranscriptomic analysisEpigenetic modifiersHeart developmentRegulated networkTranscript levelsKey regulatorMolecular mechanismsCell differentiationNeural tubePRDM6Ductus arteriosusPotential targetDifferentiation
2021
Dyrk1b promotes autophagy during skeletal muscle differentiation by upregulating 4e-bp1
Bhat N, Narayanan A, Fathzadeh M, Shah K, Dianatpour M, Abou Ziki MD, Mani A. Dyrk1b promotes autophagy during skeletal muscle differentiation by upregulating 4e-bp1. Cellular Signalling 2021, 90: 110186. PMID: 34752933, PMCID: PMC8712395, DOI: 10.1016/j.cellsig.2021.110186.Peer-Reviewed Original ResearchConceptsSkeletal muscle differentiationMuscle differentiationC2C12 cellsHuman skeletal muscle developmentSkeletal muscle developmentGlobal gene networksPost-transcriptional targetEmbryonic lethalGene networksZebrafish embryosMyofiber differentiationOverexpression approachesMuscle developmentCRISPR/DYRK1BRare gainDownstream targetsTranslational inhibitorKey regulatorUntargeted proteomicsFunction mutationsAutophagic fluxEnhances AutophagyDifferentiationAutophagyProgranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease
Zhao X, Liberti R, Jian J, Fu W, Hettinghouse A, Sun Y, Liu C. Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease. Journal Of Molecular Medicine 2021, 99: 1639-1654. PMID: 34453183, PMCID: PMC8541919, DOI: 10.1007/s00109-021-02127-6.Peer-Reviewed Original ResearchConceptsLysosomal storage diseaseGaucher diseaseAutophagosome-lysosome fusionCommon lysosomal storage diseasePGRN deficiencyNovel therapiesAnimal modelsProgranulinLC3-IIMolecular targetsCrucial mediatorCritical moleculesStorage diseaseDiseaseAutophagic fluxC-terminal fragmentImpaired fusionPatient fibroblastsAutophagyImpairmentKey regulatormTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism.
Collins S, Oh M, Sun I, Chan-Li Y, Zhao L, Powell J, Horton M. mTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism. The Journal Of Immunology 2021, 207: 913-922. PMID: 34290107, DOI: 10.4049/jimmunol.2100230.Peer-Reviewed Original ResearchConceptsKey regulatorImmune cell functionEnhanced histone acetylationCell functionRapid energy sourceClass III histoneDifferentiation of macrophagesHistone acetylationMacrophage functionMTORC1 signalingCellular metabolismOxidative phosphorylationCell metabolismMTOR signalingGlycolytic metabolismAntimicrobial compoundsGenetic deletionM2 macrophagesMouse macrophagesProper wound healingMetabolic programmingSignificant defectsM1 functionImmune cell metabolismSignalingNEDD4 regulates ubiquitination and stability of the cell adhesion molecule IGPR-1 via lysosomal pathway
Sun L, Amraei R, Rahimi N. NEDD4 regulates ubiquitination and stability of the cell adhesion molecule IGPR-1 via lysosomal pathway. Journal Of Biomedical Science 2021, 28: 35. PMID: 33962630, PMCID: PMC8103646, DOI: 10.1186/s12929-021-00731-9.Peer-Reviewed Original ResearchConceptsCell adhesion molecule IGPR-1IGPR-1Lysosomal-dependent degradationUbiquitin E3Vivo co-immunoprecipitation assaysWild-type Nedd4Knockdown of NEDD4Polyproline-rich motifCritical cellular processesCell-cell adhesionCo-immunoprecipitation assaysTreatment of cellsCell surface levelsHEK-293 cellsA375 melanoma cellsWW domainsCellular processesRich motifLysosomal pathwayC-terminusNedd4Key regulatorLysosomal inhibitorsMolecular mechanismsMelanoma cell linesTrio family proteins as regulators of cell migration and morphogenesis in development and disease – mechanisms and cellular contexts
Bircher JE, Koleske AJ. Trio family proteins as regulators of cell migration and morphogenesis in development and disease – mechanisms and cellular contexts. Journal Of Cell Science 2021, 134: jcs248393. PMID: 33568469, PMCID: PMC7888718, DOI: 10.1242/jcs.248393.Peer-Reviewed Original ResearchConceptsFamily proteinsCellular contextProtein-protein interaction domainsHuman diseasesProtein trafficking pathwaysLarge multidomain proteinCell surface receptorsTrio proteinsUNC-73Cell morphogenesisProtein traffickingTrafficking pathwaysMultidomain proteinsInteraction domainInteraction partnersKey regulatorBiological contextTissue organizationCell migrationSurface receptorsProteinTrio familiesRecent discoveryMorphogenesisRegulatorThe RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells
Wang Y, He K, Sheng B, Lei X, Tao W, Zhu X, Wei Z, Fu R, Wang A, Bai S, Zhang Z, Hong N, Ye C, Tian Y, Wang J, Li M, Zhang K, Li L, Yang H, Li HB, Flavell RA, Zhu S. The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2017432118. PMID: 33483420, PMCID: PMC7848544, DOI: 10.1073/pnas.2017432118.Peer-Reviewed Original ResearchConceptsRNA helicasesEssential biological processesPaneth cellsRNA helicase DHX15Antimicrobial protein expressionCell-specific functionsViral RNA sensorsRNA splicingHelicasesUlcerative colitis patientsCell-specific depletionDHX15Complete knockoutKey regulatorBiological processesIntestinal epithelial cellsLethality of miceVivo roleEnteric bacteriaRNA sensorsDextran sodiumColitis patientsLack of evidenceAntimicrobial responsesIntestinal inflammation
2020
Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease
Omote N, Sauler M. Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease. Frontiers In Medicine 2020, 7: 603047. PMID: 33425948, PMCID: PMC7785852, DOI: 10.3389/fmed.2020.603047.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNon-coding RNAsCellular stress responseNon-coding RNACellular senescenceCell fateChronic obstructive pulmonary diseaseStress responseAlternative cell fatesIdiopathic pulmonary fibrosisLong non-coding RNAsObstructive pulmonary diseaseCellular stressorsCellular stressKey regulatorSenescencePulmonary diseaseDNA damagePulmonary fibrosisMitochondrial dysfunctionRNACellular mechanismsChronic lung diseasePotential therapeutic roleRegulatorOxidative stressTFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9-ALS
Cunningham K, Maulding K, Ruan K, Senturk M, Grima J, Sung H, Zuo Z, Song H, Gao J, Dubey S, Rothstein J, Zhang K, Bellen H, Lloyd T. TFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9-ALS. ELife 2020, 9: e59419. PMID: 33300868, PMCID: PMC7758070, DOI: 10.7554/elife.59419.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAmyotrophic Lateral SclerosisAnimalsAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBlotting, WesternC9orf72 ProteinDisease Models, AnimalDrosophila melanogasterFemaleFluorescent Antibody TechniqueFrontotemporal DementiaHeLa CellsHumansLysosomesMaleMicrophthalmia-Associated Transcription FactorMicroscopy, Electron, TransmissionMotor CortexConceptsNucleocytoplasmic transportNuclear importC9-ALS/FTDKey transcriptional regulatorAutophagic cargo degradationNeurodegenerative disease pathogenesisLysosome-like organellesProteostasis defectsGGGGCC hexanucleotide repeat expansionTranscriptional regulatorsCargo degradationKey regulatorUbiquitinated aggregatesCytoplasmic mislocalizationHuman cellsAmyotrophic lateral sclerosisGGGGCC repeatsHexanucleotide repeat expansionRepeat expansionFrontotemporal dementiaTFEBC9-ALSAutophagyRegulatorPotent suppressorTCP5 controls leaf margin development by regulating KNOX and BEL-like transcription factors in Arabidopsis
Yu H, Zhang L, Wang W, Tian P, Wang W, Wang K, Gao Z, Liu S, Zhang Y, Irish VF, Huang T. TCP5 controls leaf margin development by regulating KNOX and BEL-like transcription factors in Arabidopsis. Journal Of Experimental Botany 2020, 72: 1809-1821. PMID: 33258902, DOI: 10.1093/jxb/eraa569.Peer-Reviewed Original ResearchConceptsTranscription factorsLeaf marginsLeaf margin developmentTCP transcription factorsSpatial-specific mannerLeaf morphogenesisLeaf serrationGene functionRedundant rolesKNAT3Key regulatorTCP5Saw1MorphogenesisMargin developmentSpecific mechanismsKey mechanismArabidopsisImportant processTranscriptionLeavesRegulatorRegulationMechanismOutgrowthTransformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease
Wang M, Li A, Sekiya M, Beckmann ND, Quan X, Schrode N, Fernando MB, Yu A, Zhu L, Cao J, Lyu L, Horgusluoglu E, Wang Q, Guo L, Wang YS, Neff R, Song WM, Wang E, Shen Q, Zhou X, Ming C, Ho SM, Vatansever S, Kaniskan HÜ, Jin J, Zhou MM, Ando K, Ho L, Slesinger PA, Yue Z, Zhu J, Katsel P, Gandy S, Ehrlich ME, Fossati V, Noggle S, Cai D, Haroutunian V, Iijima KM, Schadt E, Brennand KJ, Zhang B. Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease. Neuron 2020, 109: 257-272.e14. PMID: 33238137, PMCID: PMC7855384, DOI: 10.1016/j.neuron.2020.11.002.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseAlzheimer's diseaseKey regulatorPluripotent stem cell-derived neuronsRNAi-based knockdownStem cell-derived neuronsNovel therapeutic targetNext-generation therapeutic agentsCell-derived neuronsKey brain regionsIntegrative network analysisMulti-omics dataComplex molecular interactionsMulti-omics profilingNCH-51Neuronal impairmentGene subnetworksDisease-related processesCortical areasTherapeutic targetDrosophila modelNeuropathological phenotypeBrain regionsTherapeutic agentsMolecular mechanismsStac protein regulates release of neuropeptides
Hsu IU, Linsley JW, Zhang X, Varineau JE, Berkhoudt DA, Reid LE, Lum MC, Orzel AM, Leflein A, Xu H, Collins CA, Hume RI, Levitan ES, Kuwada JY. Stac protein regulates release of neuropeptides. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 29914-29924. PMID: 33168737, PMCID: PMC7703553, DOI: 10.1073/pnas.2009224117.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedBehavior Observation TechniquesBehavior, AnimalCalcium ChannelsDrosophila melanogasterDrosophila ProteinsFemaleIntracellular Signaling Peptides and ProteinsIntravital MicroscopyLarvaMaleModels, AnimalMotor NeuronsMuscle, SkeletalNeuromuscular JunctionNeuropeptidesOptical ImagingPatch-Clamp TechniquesPresynaptic TerminalsConceptsSTAC proteinsRelease of neuropeptidesVertebrate skeletal muscleSubset of neuronsMolecular regulationGenetic manipulationKey regulatorMotor neuronsCytosolic CaNumerous neural functionsSmall familyCentral nervous systemExcitation-contraction couplingGenesSkeletal muscleL-type CaProteinNeuropeptide releaseNervous systemNeural functionDrosophilaNeuropeptidesVertebratesNeuronsRegulator
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