2024
The cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis
McCool M, Bryant C, Abriola L, Surovtseva Y, Baserga S. The cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis. PLOS Biology 2024, 22: e3002718. PMID: 38976757, PMCID: PMC11257408, DOI: 10.1371/journal.pbio.3002718.Peer-Reviewed Original ResearchRibosome biogenesis factorsRibosome biogenesisBiogenesis factorsCell growthNucleolar functionRegulation of nucleolar functionHuman ribosome biogenesisProtein synthesisProduction of ribosomesFamily of proteinsSource of mutagenesisLevel of protein synthesisCytidine deaminase familyIncreased cell growthPromote cell growthPre-rRNAPotential direct rolePre-mRNATransient overexpressionRibosomeGenomic mutationsBiogenesisMCF10A cellsMaturation stepsAPOBEC3AA small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus
Li J, Leng L, Pantouris G, Manjula R, Piecychna M, Abriola L, Hu B, Lolis E, Armstrong M, Donnelly S, Bucala R. A small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus. Journal Of Biological Chemistry 2024, 300: 107443. PMID: 38838773, PMCID: PMC11259703, DOI: 10.1016/j.jbc.2024.107443.Peer-Reviewed Original ResearchPromoter microsatellitesGene expressionMicrosatellite repeat numberMacrophage migration inhibitory factorLength-dependent mannerRNA expression analysisSusceptibility lociFunctional variantsSmall molecule inhibitorsExpression analysisPharmacogenomic developmentRepeat numberMicrosatelliteFunctional interactionsTranscription inhibitorInflammatory gene expressionMIF mRNA expressionCytokine macrophage migration inhibitory factorTranscriptionGenesProtein expressionMigration inhibitory factorExpressionInhibitory factorExpressing macrophagesDiscovery of novel microRNA mimic repressors of ribosome biogenesis
Bryant C, McCool M, González G, Abriola L, Surovtseva Y, Baserga S. Discovery of novel microRNA mimic repressors of ribosome biogenesis. Nucleic Acids Research 2024, 52: 1988-2011. PMID: 38197221, PMCID: PMC10899765, DOI: 10.1093/nar/gkad1235.Peer-Reviewed Original Research
2023
Human nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processing
McCool M, Bryant C, Huang H, Ogawa L, Farley-Barnes K, Sondalle S, Abriola L, Surovtseva Y, Baserga S. Human nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processing. RNA Biology 2023, 20: 257-271. PMID: 37246770, PMCID: PMC10228412, DOI: 10.1080/15476286.2023.2217392.Peer-Reviewed Original ResearchConceptsPre-rRNA accumulationRibosome biogenesisNonessential roleEukaryotic ribosome biogenesisEssential cellular processesNucleolar stress responsePre-rRNA levelsRRNA processingLikely orthologCellular processesAssociated proteinsTumor suppressorStress responseHuman cellsProtein synthesisProtein 7Human counterpartBiogenesisYeastOrthologsHomologSubcomplexAccumulationRRNATranscriptionEngineered cardiac tissue model of restrictive cardiomyopathy for drug discovery
Wang B, Nash T, Zhang X, Rao J, Abriola L, Kim Y, Zakharov S, Kim M, Luo L, Morsink M, Liu B, Lock R, Fleischer S, Tamargo M, Bohnen M, Welch C, Chung W, Marx S, Surovtseva Y, Vunjak-Novakovic G, Fine B. Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery. Cell Reports Medicine 2023, 4: 100976. PMID: 36921598, PMCID: PMC10040415, DOI: 10.1016/j.xcrm.2023.100976.Peer-Reviewed Original ResearchConceptsRestrictive cardiomyopathyElevated ventricular filling pressuresVentricular filling pressurePrecision medicine approachVariety of cardiomyopathiesPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesDiastolic relaxationCardiomyocyte relaxationFilamin CMyocardial relaxationCell-derived cardiomyocytesFilling pressurePotential therapyRelaxation velocityMyocardial stiffnessCalcium kineticsMedicine approachCardiomyopathyTranslational potentialIsogenic control linesCardiac tissuePassive tensionScreening identifiesTissue model
2022
Human pre-60S assembly factors link rRNA transcription to pre-rRNA processing
McCool M, Buhagiar A, Bryant C, Ogawa L, Abriola L, Surovtseva Y, Baserga S. Human pre-60S assembly factors link rRNA transcription to pre-rRNA processing. RNA 2022, 29: rna.079149.122. PMID: 36323459, PMCID: PMC9808572, DOI: 10.1261/rna.079149.122.Peer-Reviewed Original ResearchRRNA transcriptionRRNA processingRibosomal subunit biogenesisRNA polymerase IRibosome biosynthesisSubunit biogenesisRibosome biogenesisRibosome assemblyAssembly factorsTranscription controlBiogenesis factorsRRNA productionSteady-state levelsRNA transcriptionPolymerase IComplex membersHuman cellsProtein synthesisP53 stabilizationTranscriptionEssential processBiogenesisCell proliferationDual roleRegulatory detailsRASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition.
Hunihan L, Zhao D, Lazowski H, Li M, Qian Y, Abriola L, Surovtseva YV, Muthusamy V, Tanoue LT, Rothberg BE, Schalper KA, Herbst RS, Wilson FH. RASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition. Clinical Cancer Research 2022, 28: 3091-3103. PMID: 35247929, PMCID: PMC9288503, DOI: 10.1158/1078-0432.ccr-21-4291.Peer-Reviewed Original ResearchConceptsLung adenocarcinomaSmoking historyPack-year smoking historyMinimal smoking historySubset of patientsPancreatic ductal adenocarcinoma cell linesPotential treatment strategyTight junction protein occludinJunction protein occludinWhole-exome sequencingAdenocarcinoma cell lineAdvanced malignanciesCancer Genome AtlasRaf-MEKAdvanced tumorsMultiple malignanciesTreatment strategiesKRAS mutationsTherapeutic strategiesTherapeutic targetOncogenic RAS SignalingRelated commentaryOncogenic driversMEK inhibitionOncogenic alterationsA high-throughput assay for directly monitoring nucleolar rRNA biogenesis
Bryant CJ, McCool MA, Abriola L, Surovtseva YV, Baserga SJ. A high-throughput assay for directly monitoring nucleolar rRNA biogenesis. Open Biology 2022, 12: 210305. PMID: 35078352, PMCID: PMC8790372, DOI: 10.1098/rsob.210305.Peer-Reviewed Original ResearchConceptsRibosome biogenesisRRNA biogenesisNucleolar functionSiRNA controlRNA polymerase 1Nucleolar protein fibrillarinPutative small molecule inhibitorsHigh-throughput primary screensHigh-throughput assaysSmall molecule inhibitorsProtein fibrillarinBiogenesisBMH-21Polymerase-1FibrillarinPrimary screenPrimary assayNucleoliAssaysMorphological alterationsRNAP1RibosomopathiesHitsBiological underpinningsDirect quantification
2021
Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function
Schiapparelli P, Pirman NL, Mohler K, Miranda-Herrera PA, Zarco N, Kilic O, Miller C, Shah SR, Rogulina S, Hungerford W, Abriola L, Hoyer D, Turk BE, Guerrero-Cázares H, Isaacs FJ, Quiñones-Hinojosa A, Levchenko A, Rinehart J. Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function. Cell Reports 2021, 36: 109416. PMID: 34289367, PMCID: PMC8379681, DOI: 10.1016/j.celrep.2021.109416.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell Line, TumorCell MovementCell ProliferationEscherichia coliFemaleGlioblastomaHEK293 CellsHumansMaleMice, NudeMiddle AgedPhosphorylationPhosphoserineProtein Serine-Threonine KinasesRecombinant ProteinsSignal TransductionSmall Molecule LibrariesSubstrate SpecificityWNK Lysine-Deficient Protein Kinase 1ConceptsKinase networkAuthentic post-translational modificationsGenetic code expansionPost-translational modificationsProduction of proteinsSmall molecule kinase inhibitorsKinase inhibitorsGenetic codePhosphorylated proteinsCode expansionKinase proteinWNK kinasesPhysiological functionsWNK4 kinaseBiochemical propertiesGlioblastoma cellsKinaseBacterial strainsProteinDistinct sitesPhosphoserineSPAKBacteriaCellular systemsCellsRestriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting
Sun Y, Abriola L, Niederer RO, Pedersen SF, Alfajaro MM, Silva Monteiro V, Wilen CB, Ho YC, Gilbert WV, Surovtseva YV, Lindenbach BD, Guo JU. Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2023051118. PMID: 34185680, PMCID: PMC8256030, DOI: 10.1073/pnas.2023051118.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 replicationSARS-CoV-2Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Syndrome coronavirus 2Vero E6 cellsHigh-throughput compound screenOpen reading frame 1bEffective antiviral strategiesCoronavirus 2E6 cellsAntiviral strategiesViral gene expressionCompound screenFluoroquinolone antibacterialsFrame 1bGene expressionIncreased numbers of nucleoli in a genome-wide RNAi screen reveal proteins that link the cell cycle to RNA polymerase I transcription
Ogawa LM, Buhagiar AF, Abriola L, Leland BA, Surovtseva YV, Baserga SJ. Increased numbers of nucleoli in a genome-wide RNAi screen reveal proteins that link the cell cycle to RNA polymerase I transcription. Molecular Biology Of The Cell 2021, 32: 956-973. PMID: 33689394, PMCID: PMC8108525, DOI: 10.1091/mbc.e20-10-0670.Peer-Reviewed Original ResearchConceptsRNA polymerase INumber of nucleoliRibosome biogenesisNucleolar organizer regionsPolymerase ICell cycleRNA polymerase I transcriptionPolymerase I transcriptionCell cycle regulationHigh-throughput quantitative imagingHuman diploid genomeIdentification of proteinsEukaryotic cellsG2/M phaseDiploid genomeNuclear condensatesRibosomal DNACycle regulationHuman breast epithelial cell lineBreast epithelial cell lineI transcriptionNovel regulatorEpithelial cell lineCycle progressionFunctional analysis
2020
An allosteric site on MKP5 reveals a strategy for small-molecule inhibition
Gannam Z, Min K, Shillingford SR, Zhang L, Herrington J, Abriola L, Gareiss PC, Pantouris G, Tzouvelekis A, Kaminski N, Zhang X, Yu J, Jamali H, Ellman JA, Lolis E, Anderson KS, Bennett AM. An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling 2020, 13 PMID: 32843541, PMCID: PMC7569488, DOI: 10.1126/scisignal.aba3043.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAmino Acid SequenceAnimalsCell DifferentiationCell LineDual-Specificity PhosphatasesEnzyme InhibitorsFemaleHigh-Throughput Screening AssaysHumansKineticsMiceMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesMyoblastsProtein BindingSequence Homology, Amino AcidSignal TransductionSmall Molecule LibrariesConceptsDystrophic muscle diseaseMitogen-activated protein kinaseMuscle diseaseTGF-β1Promising therapeutic targetP38 mitogen-activated protein kinaseTherapeutic strategiesTherapeutic targetSmall molecule inhibitionSmad2 phosphorylationDiseasePotential targetSmall-molecule screenInhibitorsTreatmentInhibition
2014
Identification of Inhibitors of Inositol 5‑Phosphatases through Multiple Screening Strategies
Pirruccello M, Nandez R, Idevall-Hagren O, Alcazar-Roman A, Abriola L, Berwick SA, Lucast L, Morel D, De Camilli P. Identification of Inhibitors of Inositol 5‑Phosphatases through Multiple Screening Strategies. ACS Chemical Biology 2014, 9: 1359-1368. PMID: 24742366, PMCID: PMC4076014, DOI: 10.1021/cb500161z.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDermisElectrophoretic Mobility Shift AssayEnzyme InhibitorsFibroblastsFluorescence PolarizationHigh-Throughput Screening AssaysHumansInositol Polyphosphate 5-PhosphatasesMolecular StructurePhosphatidylinositol PhosphatesPhosphoric Monoester HydrolasesRosaniline DyesSignal TransductionSmall Molecule LibrariesThiadiazolesTriazolesConceptsPhosphoinositide-metabolizing enzymesGrowth factor signalingSmall molecule modulatorsIdentification of inhibitorsFamily of enzymesMembrane traffickingActin nucleationCytoskeletal dynamicsCell cortexPhosphoinositide levelsCatalytic domainFactor signalingMolecule modulatorsHigh-throughput screeningLiving cellsSpecific inhibitorActivity assaysMembrane phospholipidsDirect interactionCell proliferationChemical scaffoldsPowerful research toolPotential therapeutic applicationsOCRLPhosphoinositide