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Integrated stress response

ABSTRACT: Comparison of genes induced during activation of the Integrated Stress Response by tunicamycin or following AP20187 induced dimerization of a Fv2E-PERK chimera in wildtype cells and cells carrying mutations in key ISR signaling molecules. Keywords: other

ORGANISM(S): Mus musculus

PROVIDER: GSE700 | GEO | 2003/10/07

SECONDARY ACCESSION(S): PRJNA87659

REPOSITORIES: GEO

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Transcription profiling of Integrated Stress Response induced by tunicamycin or following AP20187 induced dimerization of a Fv2E-PERK chimera in wildtype cells and cells carrying mutations in key ISR signaling molecules.

Project description:Comparison of genes induced during activation of the Integrated Stress Response by tunicamycin or following AP20187 induced dimerization of a Fv2E-PERK chimera in wildtype cells and cells carrying mutations in key ISR signaling molecules.

2007-12-15 | E-GEOD-700 | biostudies-arrayexpress

ISR target genes revealed by comprehensive microarray network study using Perk -/-, Atf4 -/-, eIF2a S51A mutant, Fv2E-PERK

Project description:To identify the target genes of integrated stress reponse (ISR), we have employed whole genome microarray expression in MEF cells. ISR gene setimation under ER stress condition using Perk -/-, Atf4 -/-, eIF2a S51A mutant, Fv2E-PERK MEF cells

2015-09-01 | E-GEOD-49598 | biostudies-arrayexpress

Integrated stress response couples mitochondria protein translation with oxidative stress control

Project description:Under stress conditions, cells elicit integrated stress response (ISR) to cope with intracellular and extracellular disturbances. However, its role in ischemic heart disease remains to be elucidated. Here, we show that oxygen deprivation in cardiomyocytes triggers significant changes in protein translation. Importantly, ischemia and ischemia/reoxygenation leads to suppression of protein synthesis, which is caused by activation of the PERK/eIF2α axis of ISR. At the functional level, cardiac specific elimination of PERK exacerbates cardiac response to ischemia/reperfusion whereas selective activation of PERK in the heart confers cardioprotection against reperfusion injury. Mechanistically, PERK-mediated improvement in cardiomyocyte survival depends on suppression of protein synthesis and consequently relieves energetic demand on mitochondria. We went further to show that mitochondrial complex components are targeted by protein translation suppression, which significantly diminishes mitochondria-associated production of reactive oxygen species. Indeed, pharmacological activation of ISR protects the heart from ischemia/reperfusion damage, even after the release of occluded coronary artery, highlighting clinical significance for myocardial infarction. Taken together, these findings suggest that ISR improves cell survival through selectively suppressing mitochondrial protein synthesis and reducing oxidative stress in ischemic heart disease.

2022-10-01 | GSE177078 | GEO

ISR target genes in WAT and BAT of mAP::Fv2E-PERK

Project description:To identify the target genes of integrated stress reponse (ISR) in WAT and BAT, we have employed whole genome microarray expression in WAT and BAT specific Fv2E-PERK transgenic mice. The mAP::Fv2E-PERK transgenic mice were injected by AP20187 or mock.

2015-08-05 | E-GEOD-49645 | biostudies-arrayexpress

ISR target genes in muscle of hSA::Fv2E-PERK

Project description:To identify the target genes of integrated stress reponse (ISR) in skeletal muscle, we have employed whole genome microarray expression in muscle specific Fv2E-PERK transgenic mice and C2C12 myotubes expressed in Fv2E-PERK. As a result, we identified that Fgf21 mRNA expression was commonly induced in skeletal muscle and C2C12.

2015-12-26 | GSE46548 | GEO

ISR pathway activation signatures in MEFs: GCN2 and PERK

Project description:In response to different cellular stressors, the ISR kinases, PERK, PKR, HRI and GCN2, activate downstream transcriptional programs. While the core ISR transcription program is well characterized, markers that are specific to each individual ISR kinase activation pathway are not known. To identify markers that are induced by PERK or GCN2, but not the other ISR kinases, we subjected WT, GCN2-/-, and PERK-/- MEFs to amino acid starvation (RPMI 1640 SILAC -Lys -Arg) or Thapsigargin (200nM) treatment for 6 hours to activate the GCN2 and PERK pathways, respectively and performed RNA sequencing.

2022-07-01 | GSE179559 | GEO

ISR target genes in adipose of maP2-Fv2E-PERK

Project description:To identify the target genes of integrated stress reponse (ISR) in adipose tissue, we have employed whole genome microarray expression in adipose specific Fv2E-PERK transgenic mice.

2021-04-01 | GSE149423 | GEO

Pharmacologic Activation of a Compensatory Integrated Stress Response Kinase Promotes Adaptive Mitochondrial Remodeling in Perk-deficient Cells

Project description:mRNA sequencing of WT or PERK-/- MEFs treated with the ISR activating compounds BtdCPU, Halofuginone, and Thapsigargin.

2023-09-09 | GSE227134 | GEO

ISR target genes in WAT and BAT of mAP::Fv2E-PERK

2015-08-05 | GSE49645 | GEO

Coordinated stimulation of axon regenerative and neurodegenerative transcriptional programs by Atf4 following optic nerve injury

Project description:To understand the contributions of the Integrated Stress Response (ISR) to the axon regenerative and neurodegenerative transcriptional programs activated by axon injury in the CNS, we evaluated by RNA-seq the retinal transcriptomes of conditional knockout mouse lines for components of the ISR three days after optic nerve crush injury. Prior to injury, intravitreal injection of AAV2-mTagBFP2-ires-Cre under the control of the human synapsin-1 promoter facilitated neuron-specific knockout of Eif2ak3, the gene that encodes the ER stress-responsive kinase Perk; Atf4, the gene that encodes the ISR mediator Activating transcription factor-4; or Ddit3, the gene that encodes another transcription factor that can mediate the ISR, C/ebp homologous protein, or CHOP. We compared the expression profiles of these transgenic retinas after injury to retinas from wildtype mice with and without injury to identify transcripts whose regulation by axon injury is dependent on ISR signaling.

2023-03-30 | GSE223321 | GEO

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