2017
mTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis through Post-transcriptional Control of ATF4
Park Y, Reyna-Neyra A, Philippe L, Thoreen CC. mTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis through Post-transcriptional Control of ATF4. Cell Reports 2017, 19: 1083-1090. PMID: 28494858, PMCID: PMC5811220, DOI: 10.1016/j.celrep.2017.04.042.Peer-Reviewed Original ResearchConceptsUpstream open reading framesATF4 translationTranscriptional programsProtein synthesisEukaryotic initiation factor 2 alphaInitiation factor 2 alphaPost-transcriptional controlRapamycin complex 1Open reading frameIntegrated stress responseAmino acid transportersTranscription factor 4Translation machineryTranslation repressorProtein familyReading frameMaster regulatorPromoter elementsBioinformatics analysisResponsive mRNAsAmino acid supplyStress responseMetabolic enzymesKey effectorsAcid transporters
2016
ERK and p38 MAPK Activities Determine Sensitivity to PI3K/mTOR Inhibition via Regulation of MYC and YAP
Muranen T, Selfors L, Hwang J, Gallegos L, Coloff J, Thoreen C, Kang S, Sabatini D, Mills G, Brugge J. ERK and p38 MAPK Activities Determine Sensitivity to PI3K/mTOR Inhibition via Regulation of MYC and YAP. Cancer Research 2016, 76: 7168-7180. PMID: 27913436, PMCID: PMC5161652, DOI: 10.1158/0008-5472.can-16-0155.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBlotting, WesternCell Line, TumorCell ProliferationDrug Resistance, NeoplasmExtracellular Signal-Regulated MAP KinasesFemaleFluorescent Antibody TechniqueHeterograftsHumansMAP Kinase Signaling SystemMiceMice, Inbred NODMicroscopy, ConfocalNeoplasms, ExperimentalP38 Mitogen-Activated Protein KinasesPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsProtein Kinase InhibitorsProto-Oncogene MasProto-Oncogene Proteins c-mycSignal TransductionTOR Serine-Threonine KinasesTranscription FactorsYAP-Signaling ProteinsConceptsPI3K/mTOR inhibitorMTOR inhibitorsTumor cellsPI3K/mTOR pathwayCell-targeted therapiesTranscriptional regulator c-MycPI3K/mTORAnimal tumor modelsUpregulation of MYCChronic inhibitionInhibition of p38Cellular signaling mechanismsTumor growthMTOR pathwayTumor modelAberrant activationTherapyStress kinase p38C-MycKinase p38InhibitionConstitutive ERK activityAttractive targetContext-dependent mechanismsProliferation arrest
2012
A unifying model for mTORC1-mediated regulation of mRNA translation
Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 2012, 485: 109-113. PMID: 22552098, PMCID: PMC3347774, DOI: 10.1038/nature11083.Peer-Reviewed Original Research5' Untranslated RegionsAnimalsBase SequenceCell Line, TumorEukaryotic Initiation Factor-4EEukaryotic Initiation Factor-4GGene Expression RegulationHumansMaleMechanistic Target of Rapamycin Complex 1MiceModels, BiologicalMultiprotein ComplexesNaphthyridinesNucleotide MotifsPhosphorylationProstatic NeoplasmsProtein BindingProtein BiosynthesisProteinsRibosomesRNA, MessengerTOR Serine-Threonine Kinases
2009
An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1*
Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS. An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1*. Journal Of Biological Chemistry 2009, 284: 8023-8032. PMID: 19150980, PMCID: PMC2658096, DOI: 10.1074/jbc.m900301200.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdenosine TriphosphateAnimalsAntibiotics, AntineoplasticAutophagyCarrier ProteinsCell Cycle ProteinsCell ProliferationCell SurvivalCells, CulturedDrug Resistance, NeoplasmEukaryotic Initiation FactorsImmunosuppressive AgentsMechanistic Target of Rapamycin Complex 1MiceMice, KnockoutMultienzyme ComplexesMultiprotein ComplexesPhosphoproteinsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Protein BiosynthesisProteinsRNA CapsSirolimusTOR Serine-Threonine KinasesTranscription FactorsConceptsRapamycin-resistant phosphorylationATP-competitive mammalian targetMammalian targetATP-competitive mTOR inhibitorsCell growthCap-dependent translationImpairs cell growthSuppression of autophagyDistinct complexesRapamycin kinaseCatalytic subunitKinase activityMTORC1 inhibitorMTORC2 inhibitionRapamycinAnti-cancer agentsDirect inhibitorMTOR inhibitorsInhibitorsProliferationMTORC2Torin1KinaseComplexesPhosphorylation