Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-43714E-GEOD-43713
PROVIDER: PRJNA187146 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Microarray to find ATF5 dependent genes in response to proteasome inhibition
| PRJNA187149 | ENA
Project description:Microarray to find CHOP dependent genes in response to proteasome inhibition
| PRJNA187148 | ENA
Project description:Environmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the Integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control and instead switch to a terminal outcome that features elevated expression of the transcription factor CHOP (GADD153/DDIT3). The focus of this study was to define the mechanisms by which CHOP directs gene regulatory networks that determine cell fate. We find that in response to proteasome inhibition, CHOP induces the expression of a collection of genes encoding transcription regulators, including ATF5, which is preferentially translated during eIF2 phosphorylation. Transcriptional expression of ATF5 is directly activated by both CHOP and ATF4. Knock-down of ATF5 increased cell survival in response to proteasome inhibition, supporting the idea that both ATF5 and CHOP have pro-apoptotic functions. Transcriptome analyses of ATF5-dependent genes revealed targets involved in apoptosis, including, NOXA, which is important for inducing cell death during proteasome inhibition. This study suggests that the ISR features a feed-forward loop of stress induced transcriptional regulators, each subject to transcriptional and translational control that can switch cell fate towards apoptosis. 8 plates (10cm) of WT and and 8 plates (10cm) of ATF5-KD MEF cells were subject to no stress (4 each for a total of 8) or treated for 8 hours with 1uM MG132 (4 each for a total of 8). Unstressed cells were harvested at the same time as the stressed cells
2013-09-05 | E-GEOD-43714 | biostudies-arrayexpress
Project description:Environmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the Integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control and instead switch to a terminal outcome that features elevated expression of the transcription factor CHOP (GADD153/DDIT3). The focus of this study was to define the mechanisms by which CHOP directs gene regulatory networks that determine cell fate. We find that in response to proteasome inhibition, CHOP induces the expression of a collection of genes encoding transcription regulators, including ATF5, which is preferentially translated during eIF2 phosphorylation. Transcriptional expression of ATF5 is directly activated by both CHOP and ATF4. Knock-down of ATF5 increased cell survival in response to proteasome inhibition, supporting the idea that both ATF5 and CHOP have pro-apoptotic functions. Transcriptome analyses of ATF5-dependent genes revealed targets involved in apoptosis, including, NOXA, which is important for inducing cell death during proteasome inhibition. This study suggests that the ISR features a feed-forward loop of stress induced transcriptional regulators, each subject to transcriptional and translational control that can switch cell fate towards apoptosis. 8 plates (10cm) of WT and and 8 plates (10cm) of CHOP-/- MEF cells were subject to no stress (4 each for a total of 8) or treated for 8 hours with 1uM MG132 (4 each for a total of 8). Unstressed cells were harvested at the same time as the stressed cells
2013-09-05 | E-GEOD-43713 | biostudies-arrayexpress
Project description:Microarray to find CHOP dependent genes in response to proteasome inhibition
2015-07-10 | E-GEOD-43713 | ExpressionAtlas
Project description:Environmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the Integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control and instead switch to a terminal outcome that features elevated expression of the transcription factor CHOP (GADD153/DDIT3). The focus of this study was to define the mechanisms by which CHOP directs gene regulatory networks that determine cell fate. We find that in response to proteasome inhibition, CHOP induces the expression of a collection of genes encoding transcription regulators, including ATF5, which is preferentially translated during eIF2 phosphorylation. Transcriptional expression of ATF5 is directly activated by both CHOP and ATF4. Knock-down of ATF5 increased cell survival in response to proteasome inhibition, supporting the idea that both ATF5 and CHOP have pro-apoptotic functions. Transcriptome analyses of ATF5-dependent genes revealed targets involved in apoptosis, including, NOXA, which is important for inducing cell death during proteasome inhibition. This study suggests that the ISR features a feed-forward loop of stress induced transcriptional regulators, each subject to transcriptional and translational control that can switch cell fate towards apoptosis.
2013-09-05 | GSE43714 | GEO
Project description:Environmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the Integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control and instead switch to a terminal outcome that features elevated expression of the transcription factor CHOP (GADD153/DDIT3). The focus of this study was to define the mechanisms by which CHOP directs gene regulatory networks that determine cell fate. We find that in response to proteasome inhibition, CHOP induces the expression of a collection of genes encoding transcription regulators, including ATF5, which is preferentially translated during eIF2 phosphorylation. Transcriptional expression of ATF5 is directly activated by both CHOP and ATF4. Knock-down of ATF5 increased cell survival in response to proteasome inhibition, supporting the idea that both ATF5 and CHOP have pro-apoptotic functions. Transcriptome analyses of ATF5-dependent genes revealed targets involved in apoptosis, including, NOXA, which is important for inducing cell death during proteasome inhibition. This study suggests that the ISR features a feed-forward loop of stress induced transcriptional regulators, each subject to transcriptional and translational control that can switch cell fate towards apoptosis.
2013-09-05 | GSE43713 | GEO
Project description:Microarray to find ATF5 dependent genes in response to proteasome inhibition
2015-07-10 | E-GEOD-43714 | ExpressionAtlas
Project description:The proteasome is key for maintaining cellular homeostasis by ensuring protein turnover. Proteasome inhibition triggers a compensatory increase in proteasome gene expression, but it is largely undetermined whether this is the primary response induced by proteasome inhibition. Here, we profiled the transcriptional changes induced by chemical and genetic proteasome inhibition. By examining the time-dose response to proteasome inhibition in cells and organoids, we find that modulation of proteasome gene expression varies in a context-dependent manner, and that other categories are more prominently and consistently regulated by proteasome inhibition. These include upregulation of chaperones and secreted factors, and downregulation of cell cycle regulators. Moreover, we define a proteasome stress response signature based on genes that are significantly and consistently modulated by proteasome inhibition across different cell systems. Some tissues (e.g., skeletal muscle) display an age-associated modulation of this signature consistent with age-activation of the proteasome stress response. Collectively, our study provides a global analysis of transcriptional changes induced by proteasome inhibition, and defines a transcriptional signature of proteasome stress that can be utilized to monitor the activation of this stress response.
2026-08-26 | GSE312866 | GEO
Project description:The proteasome is key for maintaining cellular homeostasis by ensuring protein turnover. Proteasome inhibition triggers a compensatory increase in proteasome gene expression, but it is largely undetermined whether this is the primary response induced by proteasome inhibition. Here, we profiled the transcriptional changes induced by chemical and genetic proteasome inhibition. By examining the time-dose response to proteasome inhibition in cells and organoids, we find that modulation of proteasome gene expression varies in a context-dependent manner, and that other categories are more prominently and consistently regulated by proteasome inhibition. These include upregulation of chaperones and secreted factors, and downregulation of cell cycle regulators. Moreover, we define a proteasome stress response signature based on genes that are significantly and consistently modulated by proteasome inhibition across different cell systems. Some tissues (e.g., skeletal muscle) display an age-associated modulation of this signature consistent with age-activation of the proteasome stress response. Collectively, our study provides a global analysis of transcriptional changes induced by proteasome inhibition, and defines a transcriptional signature of proteasome stress that can be utilized to monitor the activation of this stress response.
2026-08-26 | GSE312867 | GEO