Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.14016
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dc.titleSub-lethal oxidative stress induces lysosome biogenesis via a lysosomal membrane permeabilization-cathepsin-caspase 3-transcription factor EB-dependent pathway
dc.contributor.authorLeow S.M.
dc.contributor.authorSerene Chua S.X.
dc.contributor.authorVenkatachalam G.
dc.contributor.authorShen L.
dc.contributor.authorLuo L.
dc.contributor.authorClement M.-V.
dc.date.accessioned2020-09-01T00:58:48Z
dc.date.available2020-09-01T00:58:48Z
dc.date.issued2017
dc.identifier.citationLeow S.M., Serene Chua S.X., Venkatachalam G., Shen L., Luo L., Clement M.-V. (2017). Sub-lethal oxidative stress induces lysosome biogenesis via a lysosomal membrane permeabilization-cathepsin-caspase 3-transcription factor EB-dependent pathway. Oncotarget 8 (10) : 16170-16189. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.14016
dc.identifier.issn19492553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/173806
dc.description.abstractHere we provide evidence to link sub-lethal oxidative stress to lysosome biogenesis. Exposure of cells to sub-lethal concentrations of exogenously added hydrogen peroxide resulted in cytosol to nuclear translocation of the Transcription Factor EB (TFEB), the master controller of lysosome biogenesis and function. Nuclear translocation of TFEB was dependent upon the activation of a cathepsin-caspase 3 signaling pathway, downstream of lysosomal membrane permeabilization and accompanied by a significant increase in lysosome numbers as well as induction of TFEB-dependent lysosome-associated genes expression such as Ctsl, Lamp2 and its spliced variant Lamp2a, Neu1, Ctsb, Sqstm1, and Atg9b. The effects of sublethal oxidative stress on lysosomal gene expression and biogenesis were rescued upon gene silencing of caspase 3 and TFEB. Notably, caspase 3 activation was not associated with phenotypic hallmarks of apoptosis, evidenced by the absence of caspase 3 substrate cleavage, such as PARP, Lamin A/C or gelsolin. Taken together, these data demonstrate for the first time an unexpected and non-canonical role of a cathepsin-caspase 3 axis in the nuclear translocation of TFEB leading to lysosome biogenesis under conditions of sub-lethal oxidative stress.
dc.sourceUnpaywall 20200831
dc.subjectcaspase 3
dc.subjectcathepsin
dc.subjectgelsolin
dc.subjecthydrogen peroxide
dc.subjectlamin A
dc.subjectlamin C
dc.subjectnicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase
dc.subjecttranscription factor
dc.subjecttranscription factor EB
dc.subjectunclassified drug
dc.subjectbasic helix loop helix leucine zipper transcription factor
dc.subjectcaspase 3
dc.subjectcathepsin
dc.subjecthydrogen peroxide
dc.subjectoxidizing agent
dc.subjectTFEB protein, rat
dc.subjectanimal cell
dc.subjectapoptosis
dc.subjectArticle
dc.subjectAtg9b gene
dc.subjectbiogenesis
dc.subjectcell count
dc.subjectcell membrane permeability
dc.subjectcell nucleus
dc.subjectconcentration (parameters)
dc.subjectcontrolled study
dc.subjectCtsb gene
dc.subjectCtsl gene
dc.subjectcytosol
dc.subjectenzyme activation
dc.subjectenzyme substrate
dc.subjectgene
dc.subjectgene expression
dc.subjectgene silencing
dc.subjectgenetic variability
dc.subjectintracellular transport
dc.subjectLamp2 gene
dc.subjectLamp2a gene
dc.subjectlysosome membrane
dc.subjectNeu1 gene
dc.subjectnonhuman
dc.subjectoxidative stress
dc.subjectphenotype
dc.subjectprotein cleavage
dc.subjectprotein function
dc.subjectprotein transport
dc.subjectrat
dc.subjectRNA splicing
dc.subjectsignal transduction
dc.subjectSqstm1 gene
dc.subjectanimal
dc.subjectcell line
dc.subjectcell membrane permeability
dc.subjectcell survival
dc.subjectconfocal microscopy
dc.subjectcytology
dc.subjectdrug effects
dc.subjectgenetics
dc.subjectimmunoblotting
dc.subjectintracellular membrane
dc.subjectlysosome
dc.subjectmetabolism
dc.subjectmyoblast
dc.subjectnucleocytoplasmic transport
dc.subjectreverse transcription polymerase chain reaction
dc.subjectRNA interference
dc.subjectActive Transport, Cell Nucleus
dc.subjectAnimals
dc.subjectBasic Helix-Loop-Helix Leucine Zipper Transcription Factors
dc.subjectCaspase 3
dc.subjectCathepsins
dc.subjectCell Line
dc.subjectCell Membrane Permeability
dc.subjectCell Survival
dc.subjectGene Expression
dc.subjectHydrogen Peroxide
dc.subjectImmunoblotting
dc.subjectIntracellular Membranes
dc.subjectLysosomes
dc.subjectMicroscopy, Confocal
dc.subjectMyoblasts
dc.subjectOxidants
dc.subjectOxidative Stress
dc.subjectRats
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectRNA Interference
dc.subjectSignal Transduction
dc.typeArticle
dc.contributor.departmentBIOCHEMISTRY
dc.contributor.departmentDEAN'S OFFICE (MEDICINE)
dc.description.doi10.18632/oncotarget.14016
dc.description.sourcetitleOncotarget
dc.description.volume8
dc.description.issue10
dc.description.page16170-16189
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