2021
Insulin receptor substrate 1, but not IRS2, plays a dominant role in regulating pancreatic alpha cell function in mice
Takatani T, Shirakawa J, Shibue K, Gupta M, Kim H, Lu S, Hu J, White M, Kennedy R, Kulkarni R. Insulin receptor substrate 1, but not IRS2, plays a dominant role in regulating pancreatic alpha cell function in mice. Journal Of Biological Chemistry 2021, 296: 100646. PMID: 33839150, PMCID: PMC8131928, DOI: 10.1016/j.jbc.2021.100646.Peer-Reviewed Original ResearchConceptsAKT Ser/Thr kinaseInsulin receptor substrate (IRS) proteinsSer/Thr kinaseAlpha-cell functionGlobal protein translationCell functionInsulin receptor substrate-1Pancreatic alpha-cell functionDownstream target genesReceptor substrate-1Alpha cellsAlpha-cell lineGlucagon secretionSubstrate proteinsProtein translationTarget genesSubstrate-1Downstream proteinsDominant regulatorPancreatic alpha cellsMitochondrial dysfunctionCognate receptorsIRS2Normal glucose toleranceCell lines
2019
Functional analysis and fine mapping of the 9p22.2 ovarian cancer susceptibility locus
Buckley MA, Woods NT, Tyrer JP, Mendoza-Fandiño G, Lawrenson K, Hazelett DJ, Najafabadi HS, Gjyshi A, Carvalho RS, Lyra PC, Coetzee SG, Shen HC, Yang AW, Earp MA, Yoder S, Risch H, Chenevix-Trench G, Ramus SJ, Phelan CM, Coetzee GA, Noushmehr H, Hughes TR, Sellers TA, Goode EL, Pharoah P, Gayther SA, Monteiro A. Functional analysis and fine mapping of the 9p22.2 ovarian cancer susceptibility locus. Cancer Research 2019, 79: canres.3864.2017. PMID: 30487138, PMCID: PMC6359979, DOI: 10.1158/0008-5472.can-17-3864.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceCarcinoma, Ovarian EpithelialCell Cycle ProteinsCell Line, TumorChromosome MappingChromosomes, Human, Pair 9Cystadenocarcinoma, SerousDNA-Binding ProteinsDNA, NeoplasmFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHEK293 CellsHumansLinkage DisequilibriumOvarian NeoplasmsPolymorphism, Single NucleotideConceptsScaffold/matrix attachment regionsMatrix attachment regionsTarget genesAttachment regionsOvarian cancer susceptibility lociGenome-wide association studiesCancer risk lociLikely target genesTranscriptional regulatory elementsAllele-specific effectsDownstream target genesLikely causal variantsCancer susceptibility lociCandidate causal SNPsFine mappingRegulatory elementsLoci identifiesCausal variantsRisk lociCausal SNPsFunctional analysisAssociation studiesCancer risk genesSusceptibility lociRisk genes
2018
Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer
Weng W, Liu N, Toiyama Y, Kusunoki M, Nagasaka T, Fujiwara T, Wei Q, Qin H, Lin H, Ma Y, Goel A. Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer. Molecular Cancer 2018, 17: 16. PMID: 29382334, PMCID: PMC5791351, DOI: 10.1186/s12943-018-0767-3.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overApoptosisBiomarkers, TumorCell DeathCell ProliferationColorectal NeoplasmsDisease ProgressionFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingOncogenesPrognosisRNA InterferenceRNA, Small InterferingConceptsPIWI-interacting RNAsSmall RNA sequencingGene expression profiling resultsImportant epigenetic regulatorsDownstream target genesExpression profiling resultsCell survival pathwaysColorectal cancerPotential prognostic biomarkerTumor suppressor genePrognostic biomarkerEpigenetic regulatorsSequence complementarityNoncoding RNAsRNA sequencingTarget genesExpression profilingBiological functionsGene expressionSurvival pathwaysSuppressor geneClinical significanceDirect targetNovel oncogeneOncogenic mediators
2015
Ikaros tumor suppressor function in pre-B ALL: potential role of Ikaros target gene Ctnnd1 (IRM10P.621)
Schjerven H, Eggesbo L, Lindeman I, Muschen M. Ikaros tumor suppressor function in pre-B ALL: potential role of Ikaros target gene Ctnnd1 (IRM10P.621). The Journal Of Immunology 2015, 194: 131.19-131.19. DOI: 10.4049/jimmunol.194.supp.131.19.Peer-Reviewed Original ResearchTumor suppressor functionTarget genesSuppressor functionDNA-binding zinc fingersTumor suppressorGenome-wide expression analysisHuman preZinc finger transcription factorFinger transcription factorIndirect target genesDownstream target genesB cell developmentImportant tumor suppressorRole of IkarosProper hematopoiesisZinc fingerChIP-seqRNA-seqTranscription factorsPatient-derived preExpression analysisPotential roleIkarosGenesIkaros expression
2013
Deletion of the Transforming Growth Factor β Receptor Type II Gene in Articular Chondrocytes Leads to a Progressive Osteoarthritis‐like Phenotype in Mice
Shen J, Li J, Wang B, Jin H, Wang M, Zhang Y, Yang Y, Im H, O'Keefe R, Chen D. Deletion of the Transforming Growth Factor β Receptor Type II Gene in Articular Chondrocytes Leads to a Progressive Osteoarthritis‐like Phenotype in Mice. Arthritis & Rheumatism 2013, 65: 3107-3119. PMID: 23982761, PMCID: PMC3928444, DOI: 10.1002/art.38122.Peer-Reviewed Original ResearchMeSH KeywordsADAM ProteinsADAMTS5 ProteinAnimalsCartilage, ArticularChondrocytesCore Binding Factor Alpha 2 SubunitDisease ProgressionMatrix Metalloproteinase 13MiceMice, KnockoutOsteoarthritisPhenotypeProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSignal TransductionUp-RegulationConceptsCritical downstream target genesDownstream target genesTarget genesGrowth factor β signalingRegulation of Runx2Mouse genetic approachesLoss of TGFβType II geneGene expression analysisInhibition of TGFβDevelopment of osteoarthritisRat chondrosarcoma cellsGenetic approachesExpression analysisConditional knockout miceTGFβ signalingOsteoarthritis-like phenotypeGenesΒ signalingADAMTS5 geneReceptor type IIChondrosarcoma cellsTGFβCartilage homeostasisOA-like phenotype
2012
BCOR Is Involved in Myeloid Cell Growth Control by Regulating Hox Genes
Cao Q, Gery S, Shojaee S, Gearhart M, Bardwell V, Muschen M, Koeffler H. BCOR Is Involved in Myeloid Cell Growth Control by Regulating Hox Genes. Blood 2012, 120: 3445. DOI: 10.1182/blood.v120.21.3445.3445.Peer-Reviewed Original ResearchHox genesMyeloid cell differentiationCell differentiationCell linesIndividual Hox genesNormal hematopoiesisEssential developmental regulatorsStem cell stateOculofaciocardiodental syndromeEarly embryonic developmentCell growth controlStem cell functionTranscriptional repressive complexDownstream target genesTumor suppressor proteinGene expression profilesMesenchymal stem cell functionImmature hematopoietic cellsDevelopmental regulatorsPolycomb groupRepressive complexesHuman leukemic cell linesMost cell linesEmbryonic developmentSuppressor protein
2010
Dominant-Negative Impact of PAX5/TEL on Downstream Targets of PAX5 and Essential Pre-B Cell Receptor Genes
Iwanski G, Thoennissen N, Nakitandwe J, Lin P, Kawamata N, Nahar R, Ramezani-Rad P, Chen S, Shurtleff S, Nowak D, Ruckert C, Dugas M, Bokemeyer C, Fazio G, Biondi A, Cazzaniga G, Downing J, Müschen M, Koeffler H. Dominant-Negative Impact of PAX5/TEL on Downstream Targets of PAX5 and Essential Pre-B Cell Receptor Genes. Blood 2010, 116: 3231. DOI: 10.1182/blood.v116.21.3231.3231.Peer-Reviewed Original ResearchB cell developmentPre-BCR signalingDominant-negative impactCell developmentTarget genesReporter constructsTyrosine kinasePre-B cell receptorPax5 target genesWild-type PAX5CCAAT/enhancer binding protein alphaBruton's agammaglobulinemia tyrosine kinaseTranscription factor Pax5Downstream target genesGene expression profilesDominant negative roleBCR pathwayGene expression dataLuciferase reporter constructsEndogenous Pax5High expression levelsTranscriptional activationAffymetrix HG-U133Downstream genesExpression of PAX5Smad3 Prevents β-Catenin Degradation and Facilitates β-Catenin Nuclear Translocation in Chondrocytes*
Zhang M, Wang M, Tan X, Li TF, Zhang YE, Chen D. Smad3 Prevents β-Catenin Degradation and Facilitates β-Catenin Nuclear Translocation in Chondrocytes*. Journal Of Biological Chemistry 2010, 285: 8703-8710. PMID: 20097766, PMCID: PMC2838293, DOI: 10.1074/jbc.m109.093526.Peer-Reviewed Original ResearchConceptsBeta-catenin protein stabilityBeta-catenin nuclear translocationNuclear translocationDownstream target genesBeta-catenin proteinN-terminal regionDetailed molecular mechanismsΒ-catenin degradationTGF-beta/Smad3Β-catenin nuclear translocationProtein complexesProtein stabilityTarget genesRegulatory mechanismsSmad3 interactionMolecular mechanismsChondrocyte developmentDependent degradationNovel mechanismDependent mannerWntSmad3Growth factorTranslocationPathway
2009
Loss of Nkx3.1 leads to the activation of discrete downstream target genes during prostate tumorigenesis
Song H, Zhang B, Watson M, Humphrey P, Lim H, Milbrandt J. Loss of Nkx3.1 leads to the activation of discrete downstream target genes during prostate tumorigenesis. Oncogene 2009, 28: 3307-3319. PMID: 19597465, PMCID: PMC2746257, DOI: 10.1038/onc.2009.181.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtrophyClusterinDisease Models, AnimalDisease ProgressionDown-RegulationGene DeletionGene Expression ProfilingGene Expression Regulation, NeoplasticHomeodomain ProteinsHumansLasersMaleMiceMicrodissectionOxidoreductases Acting on Sulfur Group DonorsProstateProstatic NeoplasmsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycPTEN PhosphohydrolaseSignal TransductionThioredoxinsTranscription FactorsTranscription, GeneticTranscriptional ActivationConceptsNKX3.1 lossMolecular consequencesGene expressionProstate tumorigenesisPTEN-AKTCancer initiationProstate cancer initiationCohort of genesNumber of genesC-Myc signaling pathwayDownstream target genesHuman prostate tumorigenesisLoss of NKX3.1NKX3.1 expressionTumor suppressor geneGene expression data setsExpression data setsQuiescin Q6Transcriptional regulatorsIndependent lossesExpression of NKX3.1Laser capture microdissectionTarget genesCancer gene expression data setsSignaling pathways
2002
Mutations in the VHL gene in sporadic apparently congenital polycythemia
Pastore Y, Jelinek J, Ang S, Guan Y, Liu E, Jedlickova K, Krishnamurti L, Prchal J. Mutations in the VHL gene in sporadic apparently congenital polycythemia. Blood 2002, 101: 1591-1595. PMID: 12393546, DOI: 10.1182/blood-2002-06-1843.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultArginineAspartic AcidBase SequenceChildChild, PreschoolDNA Mutational AnalysisErythroid Precursor CellsErythropoietinFemaleHeterozygoteHomozygoteHumansLeucineLigasesMaleMutationPedigreePolycythemiaSequence Analysis, DNATryptophanTumor Suppressor ProteinsTyrosineUbiquitin-Protein LigasesValineVon Hippel-Lindau Tumor Suppressor ProteinConceptsVon Hippel-LindauVHL geneTumor suppressor von Hippel-LindauPolycythemic disordersDownstream target genesVHL mutationsHypoxia-sensing pathwayVHL functionHypoxia-inducible factor-1alphaProteosomal degradationTarget genesErythroid cellsGermline VHL mutationsCongenital polycythemiaChuvash polycythemiaVHL syndromeGenesHIF-1alphaDevelopment of tumorsFactor-1alphaElevated serum Epo levelsMutationsEPO productionAutosomal dominant disorderPathway
2001
Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5
Bibb J, Chen J, Taylor J, Svenningsson P, Nishi A, Snyder G, Yan Z, Sagawa Z, Ouimet C, Nairn A, Nestler E, Greengard P. Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 2001, 410: 376-380. PMID: 11268215, DOI: 10.1038/35066591.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCocaineCocaine-Related DisordersCorpus StriatumCyclin-Dependent Kinase 5Cyclin-Dependent KinasesDopamineDopamine and cAMP-Regulated Phosphoprotein 32Enzyme InhibitorsGene Expression Regulation, EnzymologicKinetinMaleMiceMice, TransgenicNerve Tissue ProteinsNeuronsOligonucleotide Array Sequence AnalysisPhosphoproteinsPhosphorylationProto-Oncogene Proteins c-fosPsychomotor PerformancePurinesRatsRats, Sprague-DawleyReceptors, Dopamine D1RoscovitineSignal TransductionConceptsTranscription factorsSuch transcription factorsDownstream target genesCyclin-dependent kinase 5DNA array analysisTarget genesGene expressionCocaine administrationKinase 5Inducible transgenic miceChronic exposureCdk5 inhibitorMessenger RNACocaine addictionArray analysisDopamine-mediated neurotransmissionDopamine-containing nerve terminalsMedium spiny neuronsD1 dopamine receptorsChronic cocaine administrationOverexpression of ΔFosBProteinTransgenic miceAdaptive changesSpiny neurons
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