2024
LDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments
Tang W, Luan Y, Yuan Q, Li A, Chen S, Menacherry S, Young L, Wu D. LDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments. Nature Communications 2024, 15: 3068. PMID: 38594269, PMCID: PMC11004178, DOI: 10.1038/s41467-024-47262-z.Peer-Reviewed Original ResearchConceptsLDL receptor-related protein 5Intracellular compartmentsPolyunsaturated fatty acidsProtein 5Ligand-binding repeatsBiologically important mechanismsAssociated with human healthImport mechanismExtracellular trap formationInhibit mTORC1Cell typesFatty acidsTrap formationN-3 polyunsaturated fatty acidsCompartmentProtect miceLDLAMyocardial injuryHomologyIschemia-reperfusionMTORC1LysosomesLRP6Human healthFATP2
2021
TSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism
Alesi N, Akl EW, Khabibullin D, Liu HJ, Nidhiry AS, Garner ER, Filippakis H, Lam HC, Shi W, Viswanathan SR, Morroni M, Ferguson SM, Henske EP. TSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism. Nature Communications 2021, 12: 4245. PMID: 34253722, PMCID: PMC8275687, DOI: 10.1038/s41467-021-24499-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCarcinoma, Renal CellCell NucleusCell ProliferationFemaleGene Expression RegulationHEK293 CellsHeLa CellsHumansKidney NeoplasmsLysosomesMiceMice, Inbred NODMice, SCIDMonomeric GTP-Binding ProteinsOrganelle BiogenesisPhosphorylationPhosphoserineProtein TransportProto-Oncogene ProteinsTranscription, GeneticTuberous Sclerosis Complex 2 ProteinTumor Suppressor ProteinsConceptsTranscription factor EBTSC2-deficient cellsLysosome biogenesisLysosomal biogenesisDeficient cellsRapamycin complex 1TSC1/2 complexTFEB phosphorylationTuberous sclerosis complexTSC proteinsMaster regulatorBiogenesisMechanistic targetRagCCritical regulatorFolliculinPhosphorylationDependent sitesRegulatorProteinOverexpressionTSC2 mutationsCellsGTPaseMTORC1
2016
C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling
Amick J, Roczniak-Ferguson A, Ferguson SM. C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling. Molecular Biology Of The Cell 2016, 27: 3040-3051. PMID: 27559131, PMCID: PMC5063613, DOI: 10.1091/mbc.e16-01-0003.Peer-Reviewed Original ResearchConceptsAmino acid availabilityAcid availabilityGenome-editing strategiesKO cell linesProtein complexesSubcellular localizationKnockout phenotypesC9orf72 proteinLysosomal siteBioinformatics predictionSMCR8Tumor suppressorSwollen lysosomesFunctional interactionLysosomesC9orf72 geneCell linesStructural similarityNormal functionC9orf72PhenotypeAmyotrophic lateral sclerosisBirt-HoggIntronsMTORC1Switching on mTORC1 induces neurogenesis but not proliferation in neural stem cells of young mice
Mahoney C, Feliciano DM, Bordey A, Hartman NW. Switching on mTORC1 induces neurogenesis but not proliferation in neural stem cells of young mice. Neuroscience Letters 2016, 614: 112-118. PMID: 26812181, DOI: 10.1016/j.neulet.2015.12.042.Peer-Reviewed Original ResearchConceptsNeural stem cellsSubventricular zoneNeonatal subventricular zoneWeek old miceTuberous sclerosis complexStem cellsNewborn neuroblastsYoung miceOld miceProgressive lossYoung adultsRapamycin complex 1Mechanistic targetRecent evidenceProliferative cellsMiceHyperactive mTORC1Terminal differentiationCellsMTORC1 activationProliferationActivationMTORC1NeurogenesisHyperactivity
2015
Activating the translational repressor 4E-BP or reducing S6K-GSK3β activity prevents accelerated axon growth induced by hyperactive mTOR in vivo
Gong X, Zhang L, Huang T, Lin TV, Miyares L, Wen J, Hsieh L, Bordey A. Activating the translational repressor 4E-BP or reducing S6K-GSK3β activity prevents accelerated axon growth induced by hyperactive mTOR in vivo. Human Molecular Genetics 2015, 24: 5746-5758. PMID: 26220974, PMCID: PMC4581604, DOI: 10.1093/hmg/ddv295.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAxonsCarrier ProteinsCell Cycle ProteinsCell Growth ProcessesEukaryotic Initiation FactorsFemaleGene Expression RegulationGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaMaleMechanistic Target of Rapamycin Complex 1MiceMultiprotein ComplexesPhosphoproteinsRibosomal Protein S6 Kinases, 90-kDaSignal TransductionTOR Serine-Threonine KinasesConceptsAxon growthNew therapeutic optionsMultiple axon formationTherapeutic optionsHippocampal neuronsHyperactive mTORNeurological disordersUtero electroporationAxonal connectivityGSK3β activityTranslational repressor 4E-BPEukaryotic initiation factor 4EMTOR complex 1Translational targetsInitiation factor 4EHyperactive mTORC1VivoDownstream effectorsGSK3βAxon formationLong-range connectivityDominant negative mutantLithium chlorideMTORopathiesMTORC1Phosphorylation of GATA-6 is required for vascular smooth muscle cell differentiation after mTORC1 inhibition
Xie Y, Jin Y, Merenick BL, Ding M, Fetalvero KM, Wagner RJ, Mai A, Gleim S, Tucker DF, Birnbaum MJ, Ballif BA, Luciano AK, Sessa WC, Rzucidlo EM, Powell RJ, Hou L, Zhao H, Hwa J, Yu J, Martin KA. Phosphorylation of GATA-6 is required for vascular smooth muscle cell differentiation after mTORC1 inhibition. Science Signaling 2015, 8: ra44. PMID: 25969542, PMCID: PMC4560350, DOI: 10.1126/scisignal.2005482.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationGATA6 Transcription FactorHEK293 CellsHumansMechanistic Target of Rapamycin Complex 1MiceMice, KnockoutMultiprotein ComplexesMuscle ProteinsMuscle, Smooth, VascularMyocytes, Smooth MuscleProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesConceptsGATA-6Vascular smooth muscle cell differentiationSmooth muscle cell differentiationPhosphorylation-deficient mutantDifferentiation of VSMCsRapamycin complex 1Downstream transcriptional targetsTranscription factor GATA-6Muscle cell differentiationInhibition of mTORC1VSMC hyperplasiaTransactivation of promotersTranscriptional targetsVSMC differentiationNuclear accumulationInduced phosphorylationMechanistic targetReversible differentiationCell differentiationCells undergoDrug targetsInhibition of proliferationPhosphorylationWild-type miceMTORC1Phosphorylation of eIF2α triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma
Wengrod J, Wang D, Weiss S, Zhong H, Osman I, Gardner LB. Phosphorylation of eIF2α triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma. Science Signaling 2015, 8: ra27. PMID: 25759478, PMCID: PMC4580977, DOI: 10.1126/scisignal.aaa0899.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAutophagyCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsEnzyme ActivationEukaryotic Initiation Factor-2Gene Knock-In TechniquesHumansImmunoblottingImmunohistochemistryImmunoprecipitationMass SpectrometryMechanistic Target of Rapamycin Complex 1MelanomaMicroscopy, FluorescenceMultiprotein ComplexesMutationPhosphoprotein PhosphatasesPhosphorylationProtein Serine-Threonine KinasesSirolimusTOR Serine-Threonine KinasesTunicamycinConceptsKinase complex mTORC1Amino acid-sensing systemsProtein phosphatase 6Activation of GCN2Amino acid deprivationEukaryotic initiation factorPharmacological inhibitionWild-type alleleKinase GCN2Human melanoma samplesGCN2 activationRegulatory subunitCatalytic subunitInitiation factorsPathways downstreamPP6cGCN2MTORC1PhosphorylationAutophagyMutantsMelanoma samplesSubunitsMutationsActivation
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