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AMPK activation enhances apoptotic priming and BCL2 dependence via PERK phosphorylation

ABSTRACT: gene expression profiling comparing the effect of a direct AMPK activator (GSK621) in human AML cells (MOLM-14 cell line) transduced with a non-targeted CRISPR/Cas9 RNA guide (SCR) or a EIF2AK3 (PERK) - targeting RNA guide

ORGANISM(S): Homo sapiens

PROVIDER: GSE148094 | GEO | 2021/12/21

REPOSITORIES: GEO

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AMPK activation enhances apoptotic priming and BCL2 dependence via PERK phosphorylation

Project description:AMPK activation enhances apoptotic priming and BCL2 dependence via PERK phosphorylation

| PRJNA623197 | ENA

Ablation of ER stress-linked kinase PERK in cancer cells elicits protective T cell immunity by paraptosis immunogenic cell death-induced Type-I IFN

Project description:C57BL6 wildtype mice were injected with B16F10 melanoma transduced with either untargeted sgRNA (Scramble) or PERK (EIF2AK3) knockout (KO) sgRNA. At day 17, tumors were harvested to isolate cKit+ (CD117) precursors via magnetic bead enrichment. These cKit expressing precursors were then sequenced.

2022-07-28 | GSE206783 | GEO

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

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

The PERK signaling controls myoblasts differentiation by regulating microRNA networks

Project description:By using small RNA-seq, we report microRNA profilings from Perk knockdown C2C12 cells, differentiated C2C12 cells, Atf4 overexpressed C2C12 cells, Perk knockdown P19 cells and negative control.

2021-03-01 | GSE167878 | GEO

PERK is a critical metabolic hub for immunosuppressive function in macrophages

Project description:Here we report that the Th2 cytokine IL-4 and the tumor microenvironment activated protein kinase RNA-like ER kinase (PERK) ER stress signaling cascade to promote immunosuppressive M2 activation and proliferation. Lacking PERK signaling impeded mitochondrial respiration and lipid oxidation critical for M2 macrophages. In addition, PERK activation mediated the upregulation of PSAT1 and serine biosynthesis via the downstream transcription factor ATF4.

2022-01-01 | GSE165836 | 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

Selective activation of PERK signaling mediates fibroblast education and tumor progression by a CRELD2-dependent mechanism

Project description:It is now well-accepted that cancers co-opt the microenvironment to support their growth. However, the molecular mechanisms underlying cancer-microenvironment interactions remain poorly defined. We have found that Rho-associated kinase (ROCK) activity in the epithelial component of mammary tumors selectively actuates Protein kinase R-like endoplasmic reticulum kinase (Perk), causing the recruitment and persistent education of tumor-promoting cancer-associated fibroblasts (CAFs), a key component of the cancer microenvironment. Analysis of tumors from mice and human patients identified Cysteine-rich with EGF-like domains 2 (CRELD2), as the paracrine factor underlying PERK-mediated CAF-education downstream of ROCK. CRELD2 expression was found to be regulated by ATF4 downstream of the PERK pathway and knock-down of CRELD2 prevented tumor progression, demonstrating that the paracrine ROCK-PERK-ATF4-CRELD2 axis is a promoter of breast cancer progression and suggesting new therapeutic opportunities.

2020-05-27 | PXD018253 | Pride

Comparison of gene expression profiles in hearts exposed to pressure overload (PO) with or without sildenafil treatment in PERK wild type (flx) or PERK cardiac-specific knockout 8cko) mice.

Project description:Recently, it is reported that sildenafil suppresses maturation of PO-induced miRNAs. However, the mechanism of how sildenafil coupled NO-cGMP-PKG signaling affects this maturation was not unraveled. Here, we show that PERK-mediated suppression of miRNAs by sildenafil is vital to keep mitochondrial homeostasis, using cardiac-specific PERK knockout (cko) mice.

2020-07-10 | GSE154081 | GEO

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