Cellular response to proteasome inhibition by Bortezomib
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE71145 | GEO | 2015/09/04
SECONDARY ACCESSION(S): PRJNA290443
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of the coordinated transcriptional reponse to proteasome inhibition mRNA profiles of NIH3T3 cells which stably expressing DD-sfGFP were generated by deep sequencing using Illumina HiSeq. The samples were collected from indicated timepoints after exposed to proteasome inhibition by Bortezomib.
2015-09-04 | E-GEOD-71145 | biostudies-arrayexpress
Project description:Proteasome Inhibition Targets the KMT2A Transcriptional Complex
| PRJNA640535 | ENA
Project description:Analysis of the coordinated transcriptional reponse to heat shock and ER stress
2015-09-04 | GSE65636 | 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. 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: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: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:Analysis of the coordinated transcriptional reponse to heat shock and ER stress mRNA profiles of NIH3T3 cells which stably expressing DD-sfGFP were generated by deep sequencing, in triplicate, using Illumina HiSeq. The samples were collected from indicated timepoints after exposed to either heat stress or ER stress.
2015-09-04 | E-GEOD-65636 | biostudies-arrayexpress
Project description:The 26S proteasome regulates general protein homeostasis and controls vital cellular processes, including cell division and transcriptional regulation. Cancer cells are dependent on the proper functioning of the proteasome to modulate gene expression networks that promote tumor growth. Proteasome inhibition has emerged as an effective therapeutic strategy, although mechanisms by which this approach achieves its outcomes remain unclear. We performed an integrative analysis of the transcriptome and chromatin landscape of MCF-7 breast cancer cells treated with a model proteasome inhibitor, MG132, to examine the consequences of proteasome inhibition on gene regulation. MG132 treatment initiated dynamic changes in chromatin accessibility at specific loci termed Differentially Open Chromatin Regions (DOCRs). DOCRs with increased accessibility were primarily distal to transcription start sites (TSS), while those with decreased accessibility were promoter proximal and distal to TSS. Promoter proximal DOCRs showed a unique chromatin architecture associated with distinct divergent transcription patterns. Conversely, DOCRs distal to TSS were enriched in oncogenic super enhancers that are predominantly accessible in non-basal compared to basal breast tumor subtypes. These data define distinct chromatin states and RNAPII transcription patterns, revealing molecular mechanisms by which the proteasome modulates the expression of gene networks intrinsic to breast cancer biology.
2024-03-13 | GSE241600 | GEO
Project description:The 26S proteasome regulates general protein homeostasis and controls vital cellular processes, including cell division and transcriptional regulation. Cancer cells are dependent on the proper functioning of the proteasome to modulate gene expression networks that promote tumor growth. Proteasome inhibition has emerged as an effective therapeutic strategy, although mechanisms by which this approach achieves its outcomes remain unclear. We performed an integrative analysis of the transcriptome and chromatin landscape of MCF-7 breast cancer cells treated with a model proteasome inhibitor, MG132, to examine the consequences of proteasome inhibition on gene regulation. MG132 treatment initiated dynamic changes in chromatin accessibility at specific loci termed Differentially Open Chromatin Regions (DOCRs). DOCRs with increased accessibility were primarily distal to transcription start sites (TSS), while those with decreased accessibility were promoter proximal and distal to TSS. Promoter proximal DOCRs showed a unique chromatin architecture associated with distinct divergent transcription patterns. Conversely, DOCRs distal to TSS were enriched in oncogenic super enhancers that are predominantly accessible in non-basal compared to basal breast tumor subtypes. These data define distinct chromatin states and RNAPII transcription patterns, revealing molecular mechanisms by which the proteasome modulates the expression of gene networks intrinsic to breast cancer biology.
2024-03-13 | GSE241599 | GEO