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-HoggIntronsMTORC1