2018
Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder
Gandal MJ, Zhang P, Hadjimichael E, Walker RL, Chen C, Liu S, Won H, van Bakel H, Varghese M, Wang Y, Shieh AW, Haney J, Parhami S, Belmont J, Kim M, Moran Losada P, Khan Z, Mleczko J, Xia Y, Dai R, Wang D, Yang YT, Xu M, Fish K, Hof PR, Warrell J, Fitzgerald D, White K, Jaffe AE, Peters M, Gerstein M, Liu C, Iakoucheva L, Pinto D, Geschwind D, Ashley-Koch A, Crawford G, Garrett M, Song L, Safi A, Johnson G, Wray G, Reddy T, Goes F, Zandi P, Bryois J, Jaffe A, Price A, Ivanov N, Collado-Torres L, Hyde T, Burke E, Kleiman J, Tao R, Shin J, Akbarian S, Girdhar K, Jiang Y, Kundakovic M, Brown L, Kassim B, Park R, Wiseman J, Zharovsky E, Jacobov R, Devillers O, Flatow E, Hoffman G, Lipska B, Lewis D, Haroutunian V, Hahn C, Charney A, Dracheva S, Kozlenkov A, Belmont J, DelValle D, Francoeur N, Hadjimichael E, Pinto D, van Bakel H, Roussos P, Fullard J, Bendl J, Hauberg M, Mangravite L, Peters M, Chae Y, Peng J, Niu M, Wang X, Webster M, Beach T, Chen C, Jiang Y, Dai R, Shieh A, Liu C, Grennan K, Xia Y, Vadukapuram R, Wang Y, Fitzgerald D, Cheng L, Brown M, Brown M, Brunetti T, Goodman T, Alsayed M, Gandal M, Geschwind D, Won H, Polioudakis D, Wamsley B, Yin J, Hadzic T, De La Torre Ubieta L, Swarup V, Sanders S, State M, Werling D, An J, Sheppard B, Willsey A, White K, Ray M, Giase G, Kefi A, Mattei E, Purcaro M, Weng Z, Moore J, Pratt H, Huey J, Borrman T, Sullivan P, Giusti-Rodriguez P, Kim Y, Sullivan P, Szatkiewicz J, Rhie S, Armoskus C, Camarena A, Farnham P, Spitsyna V, Witt H, Schreiner S, Evgrafov O, Knowles J, Gerstein M, Liu S, Wang D, Navarro F, Warrell J, Clarke D, Emani P, Gu M, Shi X, Xu M, Yang Y, Kitchen R, Gürsoy G, Zhang J, Carlyle B, Nairn A, Li M, Pochareddy S, Sestan N, Skarica M, Li Z, Sousa A, Santpere G, Choi J, Zhu Y, Gao T, Miller D, Cherskov A, Yang M, Amiri A, Coppola G, Mariani J, Scuderi S, Szekely A, Vaccarino F, Wu F, Weissman S, Roychowdhury T, Abyzov A. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science 2018, 362 PMID: 30545856, PMCID: PMC6443102, DOI: 10.1126/science.aat8127.Peer-Reviewed Original ResearchConceptsTranscriptome-wide association studyTranscriptome-wide characterizationPathogenic dysregulationTranscriptomic organizationDifferential splicingCoexpression networkGenetic enrichmentRegulatory regionsGenomic dataGene expressionAssociation studiesDisease locusComprehensive resourceMechanistic insightsCis effectSplicingBipolar disorderNeural-immune mechanismsMolecular pathologyTherapeutic developmentAutism spectrum disorderExpressionMajor psychiatric disordersBrain expressionDiseased brainIsoform-Level Interpretation of High-Throughput Proteomics Data Enabled by Deep Integration with RNA-seq
Carlyle B, Kitchen RR, Zhang J, Wilson R, Lam T, Rozowsky JS, Williams KR, Sestan N, Gerstein M, Nairn AC. Isoform-Level Interpretation of High-Throughput Proteomics Data Enabled by Deep Integration with RNA-seq. Journal Of Proteome Research 2018, 17: 3431-3444. PMID: 30125121, PMCID: PMC6392456, DOI: 10.1021/acs.jproteome.8b00310.Peer-Reviewed Original ResearchConceptsRNA-seqProteomic dataGene expressionLiquid chromatography-tandem mass spectrometry proteomicsTandem mass spectrometry proteomicsHigh-throughput proteomic dataTranscriptomic profiling methodsDistinct amino acid sequencesTranscript-level expressionAmino acid sequenceMass spectrometry proteomicsHEK293 cell culturesTranslatome dataMost genesProfound functional implicationsProtein isoformsAlternate isoformsGene productsAcid sequenceCellular controlBiosynthetic stateGeneration of peptidesCell typesFunctional relevanceFunctional implications
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
1999
Modulation of a calcium/calmodulin-dependent protein kinase cascade by retinoic acid during neutrophil maturation
Lawson N, Zain M, Zibello T, Picciotto M, Nairn A, Berliner N. Modulation of a calcium/calmodulin-dependent protein kinase cascade by retinoic acid during neutrophil maturation. Experimental Hematology 1999, 27: 1682-1690. PMID: 10560916, DOI: 10.1016/s0301-472x(99)00108-3.Peer-Reviewed Original ResearchConceptsKinase cascadeCaM kinase cascadeNeutrophil maturationRetinoic acidDependent protein kinase kinase alphaWestern analysisProtein kinase cascadeSpecific gene expressionImmediate early fashionNeutrophil-specific gene expressionTrans retinoic acidNeutrophil progenitor cellsRetinoic acid receptorsNeutrophil functionUninduced cellsGene expressionKinase alphaMyeloid cellsVitamin AAcid receptorsRetinoid signalingCell typesEffect of calciumProgenitor cellsProtein levelsModulation of GT-1 DNA-binding activity by calcium-dependent phosphorylation
Maréchal E, Hiratsuka K, Delgado J, Nairn A, Qin J, Chait B, Chua N. Modulation of GT-1 DNA-binding activity by calcium-dependent phosphorylation. Plant Molecular Biology 1999, 40: 373-386. PMID: 10437822, DOI: 10.1023/a:1006131330930.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsArabidopsisBase SequenceBinding SitesCalciumCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesDNA PrimersDNA-Binding ProteinsIn Vitro TechniquesMolecular Sequence DataNuclear ProteinsPhosphorylationPlants, ToxicRatsRecombinant ProteinsSequence Homology, Amino AcidSubstrate SpecificityTranscription FactorsConceptsDNA-binding activityCalcium-dependent phosphorylationGene expressionMolecular switchGT-1Analysis of mutantsDNA-binding proteinsLight-grown plantsPost-translational modificationsCalf intestine phosphataseCalcium/calmodulin kinasePhosphorylatable residuesCasein kinaseGene activationMass spectrometry analysisPromoter sequencesDNA bindingKinase activityBoxIICalmodulin kinasePhosphorylationHGT-1Novo synthesisDephosphorylationSpectrometry analysis
1992
Increased phosphorylation of elongation factor 2 in Alzheimer's disease
Johnson G, Gotlib J, Haroutunian V, Bierer L, Nairn A, Merril C, Wallace W. Increased phosphorylation of elongation factor 2 in Alzheimer's disease. Brain Research 1992, 15: 319-326. PMID: 1331687, DOI: 10.1016/0169-328x(92)90124-t.Peer-Reviewed Original ResearchConceptsDisease brainAlzheimer's diseaseAlzheimer's disease brainFactor 2AD homogenatesAD tissueElongation factor 2Brain homogenatesSame brainDiseaseVariant isoformsProtein synthesisPhosphorylated formInhibits protein synthesisBrainUnaffected areasHomogenatesAcidic isoformsPhosphorylationGene expressionEF-2