2024
SUMO-specific protease 1 regulates germinal center B cell response through deSUMOylation of PAX5
Qi J, Yan L, Sun J, Huang C, Su B, Cheng J, Shen L. SUMO-specific protease 1 regulates germinal center B cell response through deSUMOylation of PAX5. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314619121. PMID: 38776375, PMCID: PMC11145296, DOI: 10.1073/pnas.2314619121.Peer-Reviewed Original ResearchConceptsPaired box protein 5GC B cellsSUMO-specific protease 1Activation-induced cytidine deaminaseProtein SUMOylationClass switch recombinationProtein stabilityB cellsProtease 1B cell responsesProtein 5Cytidine deaminaseSENP1Up-regulatedGC B cell responsesSomatic hypermutationSUMOylationDeSUMOylationGerminal centersHigher affinityProduction of class-switched antibodiesGerminal center B cell responsesGC reactionMemory B cellsClass-switched antibodiesPROTAC EZH2 degrader-1 overcomes the resistance of podophyllotoxin derivatives in refractory small cell lung cancer with leptomeningeal metastasis
Shi M, Ding X, Tang L, Cao W, Su B, Zhang J. PROTAC EZH2 degrader-1 overcomes the resistance of podophyllotoxin derivatives in refractory small cell lung cancer with leptomeningeal metastasis. BMC Cancer 2024, 24: 504. PMID: 38644473, PMCID: PMC11034131, DOI: 10.1186/s12885-024-12244-3.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerCell lung cancerMouse modelLung cancerRefractory small cell lung cancerNude miceIn vivo drug testingCell linesDrug testingLM cellsSensitivity of cisplatinIn vitro drug testingIncreased in vitroBackgroundLeptomeningeal metastasisLeptomeningeal metastasesSevere neurological disordersAssociated with several neurological disordersDrug sensitivityIn vivo live imagingHistological examinationCarotid arteryEffective treatmentMetastasisDrug trialsExpressing luciferase
2022
Nebulization of risedronate alleviates airway obstruction and inflammation of chronic obstructive pulmonary diseases via suppressing prenylation-dependent RAS/ERK/NF-κB and RhoA/ROCK1/MLCP signaling
Liu D, Xu W, Tang Y, Cao J, Chen R, Wu D, Chen H, Su B, Xu J. Nebulization of risedronate alleviates airway obstruction and inflammation of chronic obstructive pulmonary diseases via suppressing prenylation-dependent RAS/ERK/NF-κB and RhoA/ROCK1/MLCP signaling. Respiratory Research 2022, 23: 380. PMID: 36575527, PMCID: PMC9795678, DOI: 10.1186/s12931-022-02274-5.Peer-Reviewed Original ResearchConceptsAirway smooth muscle cellsAirway obstructionB2 agonistsObstructive pulmonary diseaseLung inflammationCOPD ratsInflammation of chronic obstructive pulmonary diseaseExpression of B2 receptorsLung depositionPulmonary diseaseTumor necrosis factor-alphaFirst-line treatmentNecrosis factor-alphaTreating COPD patientsChronic obstructive pulmonary diseaseSmooth muscle cellsTreatment of COPDBackgroundChronic obstructive pulmonary diseaseNitrogen-containing bisphosphonatesProgression of COPDLung function declineLong-term useRisedronate treatmentASMCs relaxationAntimuscarinic drugs
2011
MEKK3 Regulates IFN-γ Production in T Cells through the Rac1/2-Dependent MAPK Cascades
Wang X, Zhang F, Chen F, Liu D, Zheng Y, Zhang Y, Dong C, Su B. MEKK3 Regulates IFN-γ Production in T Cells through the Rac1/2-Dependent MAPK Cascades. The Journal Of Immunology 2011, 186: 5791-5800. PMID: 21471448, PMCID: PMC3833674, DOI: 10.4049/jimmunol.1002127.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAminoquinolinesAnimalsCD4-Positive T-LymphocytesCell LineFlow CytometryImmunoblottingInterferon-gammaInterleukin-12Interleukin-18Listeria monocytogenesMAP Kinase Kinase Kinase 3MAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein KinasesPyrimidinesRac GTP-Binding ProteinsRac1 GTP-Binding ProteinReceptors, Antigen, T-CellConceptsSer/Thr proteinMAPK activationMAPK kinase kinase (MAP3K) familyP38 MAPK activationThr proteinMAPK cascadeKinase familyMAPK signalsConditional knockout miceMEKK3 activationMEKK3 deficiencyMEKK3Cell differentiationTCR stimulationTCR signalsTh2 cell differentiationSpecific roleBacterial infectionsT cellsCellsKnockout miceActivationJNKProductionProteinThe Kinases MEKK2 and MEKK3 Regulate Transforming Growth Factor-β-Mediated Helper T Cell Differentiation
Chang X, Liu F, Wang X, Lin A, Zhao H, Su B. The Kinases MEKK2 and MEKK3 Regulate Transforming Growth Factor-β-Mediated Helper T Cell Differentiation. Immunity 2011, 34: 201-212. PMID: 21333552, PMCID: PMC3073014, DOI: 10.1016/j.immuni.2011.01.017.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCell DifferentiationEnzyme ActivationForkhead Transcription FactorsLymphocyte CountLymphopeniaMAP Kinase Kinase Kinase 2MAP Kinase Kinase Kinase 3MAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhosphorylationProtein Processing, Post-TranslationalProtein Structure, TertiaryReceptors, Antigen, T-CellSmad2 ProteinSmad3 ProteinSpecific Pathogen-Free OrganismsT-Lymphocytes, Helper-InducerT-Lymphocytes, RegulatoryTh17 CellsTransforming Growth Factor betaConceptsTh cell differentiationSevere experimental autoimmune encephalomyelitisGrowth factorExperimental autoimmune encephalomyelitisHelper T cell differentiationT helper cell differentiationCell differentiationT cell differentiationTGF-β signaling pathwaysTransforming Growth FactorHelper cell differentiationTGF-β stimulationCell receptor signalsAutoimmune encephalomyelitisTGF-β responseAbnormal accumulationImpaired phosphorylationReceptor signalsSignaling pathwaysMiceCellsKinase MEKK2DifferentiationWild-type cellsTregsmTOR Complex 2 Targets Akt for Proteasomal Degradation via Phosphorylation at the Hydrophobic Motif*
Wu YT, Ouyang W, Lazorchak AS, Liu D, Shen HM, Su B. mTOR Complex 2 Targets Akt for Proteasomal Degradation via Phosphorylation at the Hydrophobic Motif*. Journal Of Biological Chemistry 2011, 286: 14190-14198. PMID: 21321111, PMCID: PMC3077620, DOI: 10.1074/jbc.m111.219923.Peer-Reviewed Original ResearchConceptsAkt Ser-473 phosphorylationSer-473 phosphorylationAkt activationMotif phosphorylationHydrophobic motifProteasomal degradationHydrophobic motif phosphorylationLys-48-linked polyubiquitinationPhosphorylation-dependent ubiquitinationRapid proteasomal degradationProtein kinase AktRapamycin complex 2Protein life cycleDiverse human diseasesFull Akt activationActivity of AktNegative feedback regulationCellular stimuliKinase AktDependent phosphorylationProtein degradationTarget AktAkt activityHuman diseasesAkt protein
2010
Sin1-mTORC2 Suppresses rag and il7r Gene Expression through Akt2 in B Cells
Lazorchak AS, Liu D, Facchinetti V, Di Lorenzo A, Sessa WC, Schatz DG, Su B. Sin1-mTORC2 Suppresses rag and il7r Gene Expression through Akt2 in B Cells. Molecular Cell 2010, 39: 433-443. PMID: 20705244, PMCID: PMC2957800, DOI: 10.1016/j.molcel.2010.07.031.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsB-LymphocytesCell Line, TransformedDNA-Binding ProteinsForkhead Box Protein O1Forkhead Transcription FactorsGene Expression RegulationGene Rearrangement, B-LymphocyteHomeodomain ProteinsMiceMice, KnockoutPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, Interleukin-7Signal TransductionTOR Serine-Threonine KinasesTranscription FactorsConceptsB cell developmentGene expressionCell developmentRAG gene expressionMTOR complex 2FOXO1 transcriptional activityPI3K signalingMTOR inhibitor rapamycinTranscriptional activityKey regulatorB cellsMolecular mechanismsInhibitor rapamycinK signalingCell survivalFoxO1 phosphorylationMammalian targetRecombinase activityPI3KIL-7 receptorAkt2SignalingRapamycinExpressionCells
2009
MEKK3 Is Essential for Lymphopenia-Induced T Cell Proliferation and Survival
Wang X, Chang X, Facchinetti V, Zhuang Y, Su B. MEKK3 Is Essential for Lymphopenia-Induced T Cell Proliferation and Survival. The Journal Of Immunology 2009, 182: 3597-3608. PMID: 19265138, PMCID: PMC2923428, DOI: 10.4049/jimmunol.0803738.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationCell ProliferationCell SurvivalCells, CulturedGene Knock-In TechniquesHomeostasisLymphopeniaMAP Kinase Kinase Kinase 3MiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Thymus GlandConceptsT cell proliferationT cell homeostasisT cellsCell proliferationPeripheral T cell numbersSelf-peptide MHCTCR stimulationT cell immunityT cell numbersThymic T cell developmentConditional knockout miceCell homeostasisT cell developmentCell immunityActivity of ERK1/2Knockout miceConditional ablationPeptide-MHCP38 MAPKLymphopeniaCell numberSignificant reductionCell developmentSelective roleProliferation
2008
The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C
Facchinetti V, Ouyang W, Wei H, Soto N, Lazorchak A, Gould C, Lowry C, Newton AC, Mao Y, Miao RQ, Sessa WC, Qin J, Zhang P, Su B, Jacinto E. The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. The EMBO Journal 2008, 27: 1932-1943. PMID: 18566586, PMCID: PMC2486276, DOI: 10.1038/emboj.2008.120.Peer-Reviewed Original ResearchConceptsTarget of rapamycinProtein kinase CTOR complex 1Functions of TORRapamycin-sensitive TOR complex 1Site phosphorylationKinase CTurn motif siteProtein synthesisStability of AktConventional protein kinase CTORC2 functionTOR functionTOR pathwayPhosphorylation of AktHM siteKinase domainProtein foldingMotif sitesProteasome degradationNovel functionBasic residuesMammalian targetPhosphorylationAkt
2007
MEKK3 is required for endothelium function but is not essential for tumor growth and angiogenesis
Deng Y, Yang J, McCarty M, Su B. MEKK3 is required for endothelium function but is not essential for tumor growth and angiogenesis. American Journal Of Physiology - Cell Physiology 2007, 293: c1404-c1411. PMID: 17687003, DOI: 10.1152/ajpcell.00058.2007.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-1AnimalsAortaApoptosisCell ProliferationEmbryo, MammalianEndocardiumEndothelial CellsEndothelium, VascularFemaleMAP Kinase Kinase Kinase 3MiceMice, Inbred StrainsMice, KnockoutMice, NudeMitogen-Activated Protein KinasesMyocardiumNeoplasms, ExperimentalNeoplastic Stem CellsNeovascularization, PathologicPhosphorylationReceptor, TIE-2Vascular Endothelial Growth Factor AConceptsEmbryonic angiogenesisProtein kinase kinase kinase 3Embryonic stem cell linesEarly embryonic developmentCell proliferationStem cell linesTumor angiogenesisTumor growthEmbryonic developmentEndothelial cellsKinase 3ERK5 activationMEKK3Endothelial cell proliferationAng1/Tie2Essential roleCell linesProduction of VEGFCritical roleEmbryosAngiogenesisFactor productionProliferationGrowthCells
2006
SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity
Jacinto E, Facchinetti V, Liu D, Soto N, Wei S, Jung SY, Huang Q, Qin J, Su B. SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity. Cell 2006, 127: 125-137. PMID: 16962653, DOI: 10.1016/j.cell.2006.08.033.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCells, CulturedFibroblastsForkhead Box Protein O1Forkhead Box Protein O3Forkhead Transcription FactorsGene SilencingHumansMiceMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesPhosphoproteinsPhosphorylationProtein KinasesProteinsProto-Oncogene Proteins c-aktRapamycin-Insensitive Companion of mTOR ProteinRegulatory-Associated Protein of mTORSignal TransductionSubstrate SpecificityThreonineTOR Serine-Threonine KinasesTranscription FactorsConceptsAkt Ser473 phosphorylationAkt targetsSer473 phosphorylationAkt/PKB Ser473 phosphorylationPKB Ser473 phosphorylationRecent biochemical studiesTORC2 functionTORC1 functionHydrophobic motifProtein complexesRaptor-mTORMTOR functionActivation loopPhosphorylation sitesAkt functionSubstrate specificityComplex integrityS6KRegulatory mechanismsCell survivalPhosphorylationMammalian targetPhysiological importanceAkt phosphorylationBiochemical studies
2005
Identification of MEKK2/3 serine phosphorylation site targeted by the Toll‐like receptor and stress pathways
Zhang D, Facchinetti V, Wang X, Huang Q, Qin J, Su B. Identification of MEKK2/3 serine phosphorylation site targeted by the Toll‐like receptor and stress pathways. The EMBO Journal 2005, 25: 97-107. PMID: 16362041, PMCID: PMC1356356, DOI: 10.1038/sj.emboj.7600913.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, Phospho-SpecificCytokinesEnzyme ActivationInterleukin-6LigandsLipopolysaccharidesMAP Kinase Kinase Kinase 2MAP Kinase Kinase Kinase 3Molecular Sequence DataMutationPhosphoamino AcidsPhosphorylationProtein Kinase InhibitorsSerineTNF Receptor-Associated Factor 6Toll-Like Receptor 4Toll-Like ReceptorsConceptsPhosphorylation sitesSerine phosphorylationMitogen-activated protein kinase kinase kinase (MAP3K) familyMolecular mechanismsProtein kinase kinase kinase familyToll-like receptorsStress pathwaysRegulatory phosphorylation sitesSerine phosphorylation sitesCellular stress responseCellular stress pathwaysNovel molecular mechanismDifferent cellular responsesKey adaptor moleculeMEKK3 phosphorylationRegulatory serineKinase familyAdaptor moleculeStress responseCellular responsesK activationMAPK agonistsPhosphorylationMEKK2Pathway