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https://doi.org/10.18632/oncotarget.14016
Title: | Sub-lethal oxidative stress induces lysosome biogenesis via a lysosomal membrane permeabilization-cathepsin-caspase 3-transcription factor EB-dependent pathway | Authors: | Leow S.M. Serene Chua S.X. Venkatachalam G. Shen L. Luo L. Clement M.-V. |
Keywords: | caspase 3 cathepsin gelsolin hydrogen peroxide lamin A lamin C nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase transcription factor transcription factor EB unclassified drug basic helix loop helix leucine zipper transcription factor caspase 3 cathepsin hydrogen peroxide oxidizing agent TFEB protein, rat animal cell apoptosis Article Atg9b gene biogenesis cell count cell membrane permeability cell nucleus concentration (parameters) controlled study Ctsb gene Ctsl gene cytosol enzyme activation enzyme substrate gene gene expression gene silencing genetic variability intracellular transport Lamp2 gene Lamp2a gene lysosome membrane Neu1 gene nonhuman oxidative stress phenotype protein cleavage protein function protein transport rat RNA splicing signal transduction Sqstm1 gene animal cell line cell membrane permeability cell survival confocal microscopy cytology drug effects genetics immunoblotting intracellular membrane lysosome metabolism myoblast nucleocytoplasmic transport reverse transcription polymerase chain reaction RNA interference Active Transport, Cell Nucleus Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Caspase 3 Cathepsins Cell Line Cell Membrane Permeability Cell Survival Gene Expression Hydrogen Peroxide Immunoblotting Intracellular Membranes Lysosomes Microscopy, Confocal Myoblasts Oxidants Oxidative Stress Rats Reverse Transcriptase Polymerase Chain Reaction RNA Interference Signal Transduction |
Issue Date: | 2017 | 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 | 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. | Source Title: | Oncotarget | URI: | https://scholarbank.nus.edu.sg/handle/10635/173806 | ISSN: | 19492553 | DOI: | 10.18632/oncotarget.14016 |
Appears in Collections: | Staff Publications Elements |
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