Plasticity of the Mammalian Integrated Stress Response [eIF2B5]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1114733 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Plasticity of the Mammalian Integrated Stress Response [atf4]
| PRJNA1114729 | ENA
Project description:Plasticity of the Mammalian Integrated Stress Response [eIF2B5_eIF4E]
| PRJNA1114731 | ENA
Project description:Decreased nucleotide exchange activity of the eukaryotic translation initiation factor eIF2B coupled with increased phosphorylation of eIF2alpha (eIF2alpha-p) is a hallmark of the “canonical” integrated stress response (c-ISR). In mammals, however, it is unclear whether decreased eIF2B activity in absence of alterations in eIF2alpha-p which occurs in human disease including leukodystrophies, is synonymous to c-ISR. Herein, we describe a previously unknown mechanism of adaptation to decreased eIF2B activity, distinct from c-ISR, which we term “split” ISR (s-ISR). We demonstrate that s-ISR comprises translation reprogramming of only a subset of c-ISR mRNA targets which is accompanied by distinct transcriptomes. In contrast to c-ISR, s-ISR requires eIF4E-dependent translation of the upstream open reading frame 1 and subsequent stabilization of ATF4 mRNA. This is followed by altered expression of a subset of metabolic genes (e.g., PCK2), resulting in metabolic adaptations to maintain cellular bioenergetics under conditions of low eIF2B activity. Overall, these data demonstrate hitherto-unappreciated plasticity of the mammalian ISR, whereby the loss of eIF2B activity in the absence of increased eIF2-p, activates an eIF4E/ATF4/PCK2 axis to maintain energy homeostasis.
2025-01-22 | GSE268132 | GEO
Project description:Decreased nucleotide exchange activity of the eukaryotic translation initiation factor eIF2B coupled with increased phosphorylation of eIF2alpha (eIF2alpha-p) is a hallmark of the “canonical” integrated stress response (c-ISR). In mammals, however, it is unclear whether decreased eIF2B activity in absence of alterations in eIF2alpha-p which occurs in human disease including leukodystrophies, is synonymous to c-ISR. Herein, we describe a previously unknown mechanism of adaptation to decreased eIF2B activity, distinct from c-ISR, which we term “split” ISR (s-ISR). We demonstrate that s-ISR comprises translation reprogramming of only a subset of c-ISR mRNA targets which is accompanied by distinct transcriptomes. In contrast to c-ISR, s-ISR requires eIF4E-dependent translation of the upstream open reading frame 1 and subsequent stabilization of ATF4 mRNA. This is followed by altered expression of a subset of metabolic genes (e.g., PCK2), resulting in metabolic adaptations to maintain cellular bioenergetics under conditions of low eIF2B activity. Overall, these data demonstrate hitherto-unappreciated plasticity of the mammalian ISR, whereby the loss of eIF2B activity in the absence of increased eIF2-p, activates an eIF4E/ATF4/PCK2 axis to maintain energy homeostasis.
2025-01-22 | GSE268127 | GEO
Project description:Decreased nucleotide exchange activity of the eukaryotic translation initiation factor eIF2B coupled with increased phosphorylation of eIF2alpha (eIF2alpha-p) is a hallmark of the “canonical” integrated stress response (c-ISR). In mammals, however, it is unclear whether decreased eIF2B activity in absence of alterations in eIF2alpha-p which occurs in human disease including leukodystrophies, is synonymous to c-ISR. Herein, we describe a previously unknown mechanism of adaptation to decreased eIF2B activity, distinct from c-ISR, which we term “split” ISR (s-ISR). We demonstrate that s-ISR comprises translation reprogramming of only a subset of c-ISR mRNA targets which is accompanied by distinct transcriptomes. In contrast to c-ISR, s-ISR requires eIF4E-dependent translation of the upstream open reading frame 1 and subsequent stabilization of ATF4 mRNA. This is followed by altered expression of a subset of metabolic genes (e.g., PCK2), resulting in metabolic adaptations to maintain cellular bioenergetics under conditions of low eIF2B activity. Overall, these data demonstrate hitherto-unappreciated plasticity of the mammalian ISR, whereby the loss of eIF2B activity in the absence of increased eIF2-p, activates an eIF4E/ATF4/PCK2 axis to maintain energy homeostasis.
2025-01-22 | GSE268130 | GEO
Project description:OMA1, DELE1 and HRI relay mitochondrial stress to the mammalian integrated stress response
| PRJNA557038 | ENA
Project description:The goal of this study is to understand how mamalian cells respond to the mitochondial stress. Using Quant-seq, we identifed an integrated stress response signature in the cells with compromized mitochondria. Furthermore, using an unbiased CRISPRi genetic screen, we uncovered a novel signaling pathway, in which OMA1, DELE1 and HRI are three major players that relay the mitochondrial stress to the integated stress response. To further study the cellular response in the absence of this pathway, we again used Quant-seq to uncover alternative pathways that might play a role during the mitochondrial stress response.
2019-07-29 | GSE134986 | GEO
Project description:The Integrated Stress Response Promotes Macrophage Inflammation
| PRJNA1165269 | ENA
Project description:eIF3d controls the persistent integrated stress response
| PRJNA989225 | ENA
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. Keywords: other
2003-10-07 | GSE700 | GEO