Please use this identifier to cite or link to this item:
https://doi.org/10.18632/oncotarget.14016
DC Field | Value | |
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dc.title | Sub-lethal oxidative stress induces lysosome biogenesis via a lysosomal membrane permeabilization-cathepsin-caspase 3-transcription factor EB-dependent pathway | |
dc.contributor.author | Leow S.M. | |
dc.contributor.author | Serene Chua S.X. | |
dc.contributor.author | Venkatachalam G. | |
dc.contributor.author | Shen L. | |
dc.contributor.author | Luo L. | |
dc.contributor.author | Clement M.-V. | |
dc.date.accessioned | 2020-09-01T00:58:48Z | |
dc.date.available | 2020-09-01T00:58:48Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Leow 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.issn | 19492553 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/173806 | |
dc.description.abstract | Here 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.source | Unpaywall 20200831 | |
dc.subject | caspase 3 | |
dc.subject | cathepsin | |
dc.subject | gelsolin | |
dc.subject | hydrogen peroxide | |
dc.subject | lamin A | |
dc.subject | lamin C | |
dc.subject | nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase | |
dc.subject | transcription factor | |
dc.subject | transcription factor EB | |
dc.subject | unclassified drug | |
dc.subject | basic helix loop helix leucine zipper transcription factor | |
dc.subject | caspase 3 | |
dc.subject | cathepsin | |
dc.subject | hydrogen peroxide | |
dc.subject | oxidizing agent | |
dc.subject | TFEB protein, rat | |
dc.subject | animal cell | |
dc.subject | apoptosis | |
dc.subject | Article | |
dc.subject | Atg9b gene | |
dc.subject | biogenesis | |
dc.subject | cell count | |
dc.subject | cell membrane permeability | |
dc.subject | cell nucleus | |
dc.subject | concentration (parameters) | |
dc.subject | controlled study | |
dc.subject | Ctsb gene | |
dc.subject | Ctsl gene | |
dc.subject | cytosol | |
dc.subject | enzyme activation | |
dc.subject | enzyme substrate | |
dc.subject | gene | |
dc.subject | gene expression | |
dc.subject | gene silencing | |
dc.subject | genetic variability | |
dc.subject | intracellular transport | |
dc.subject | Lamp2 gene | |
dc.subject | Lamp2a gene | |
dc.subject | lysosome membrane | |
dc.subject | Neu1 gene | |
dc.subject | nonhuman | |
dc.subject | oxidative stress | |
dc.subject | phenotype | |
dc.subject | protein cleavage | |
dc.subject | protein function | |
dc.subject | protein transport | |
dc.subject | rat | |
dc.subject | RNA splicing | |
dc.subject | signal transduction | |
dc.subject | Sqstm1 gene | |
dc.subject | animal | |
dc.subject | cell line | |
dc.subject | cell membrane permeability | |
dc.subject | cell survival | |
dc.subject | confocal microscopy | |
dc.subject | cytology | |
dc.subject | drug effects | |
dc.subject | genetics | |
dc.subject | immunoblotting | |
dc.subject | intracellular membrane | |
dc.subject | lysosome | |
dc.subject | metabolism | |
dc.subject | myoblast | |
dc.subject | nucleocytoplasmic transport | |
dc.subject | reverse transcription polymerase chain reaction | |
dc.subject | RNA interference | |
dc.subject | Active Transport, Cell Nucleus | |
dc.subject | Animals | |
dc.subject | Basic Helix-Loop-Helix Leucine Zipper Transcription Factors | |
dc.subject | Caspase 3 | |
dc.subject | Cathepsins | |
dc.subject | Cell Line | |
dc.subject | Cell Membrane Permeability | |
dc.subject | Cell Survival | |
dc.subject | Gene Expression | |
dc.subject | Hydrogen Peroxide | |
dc.subject | Immunoblotting | |
dc.subject | Intracellular Membranes | |
dc.subject | Lysosomes | |
dc.subject | Microscopy, Confocal | |
dc.subject | Myoblasts | |
dc.subject | Oxidants | |
dc.subject | Oxidative Stress | |
dc.subject | Rats | |
dc.subject | Reverse Transcriptase Polymerase Chain Reaction | |
dc.subject | RNA Interference | |
dc.subject | Signal Transduction | |
dc.type | Article | |
dc.contributor.department | BIOCHEMISTRY | |
dc.contributor.department | DEAN'S OFFICE (MEDICINE) | |
dc.description.doi | 10.18632/oncotarget.14016 | |
dc.description.sourcetitle | Oncotarget | |
dc.description.volume | 8 | |
dc.description.issue | 10 | |
dc.description.page | 16170-16189 | |
Appears in Collections: | Staff Publications Elements |
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