Transcriptomic analysis of glioblastoma cells bearing different IRE1a mutants
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA421725 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Glioblastoma multiforme is the most lethal form of glioma with an overall survival at 5 years nearly null, which mainly results from acquired resistance to therapies. Large scale sequencing studies on human cancer biopsies defined IRE1alpha as the fifth most oncogenic mutated kinase in human cancer. IRE1alpha is a major component of the Unfolded Protein Response signaling and increasing evidence suggests that it is a central player in GBM development.
2017-12-09 | GSE107859 | GEO
Project description:IRE1a and XBP1 are key regulators of the unfolded protein response (UPR). XBP1 ablation causes profound hypolipidemia in mice, and triggers feedback activation of its upstream enzyme IRE1a, instigating regulated IRE1-dependent decay (RIDD), an mRNA degradation mechanism dependent on IRE1a's endoribonuclease activity. Comprehensive microarray analysis of XBP1 and/or IRE1a deficient liver identified genes involved in lipogenesis and lipoprotein metabolism as RIDD substrates, which might contribute to the suppression of plasma lipid levels by activated IRE1a. To identify RIDD substrate mRNAs and direct XBP1 targets in the liver, we performed a comprehensive comparative microarray analysis of three groups of RNA samples: WT and XBP1 deficient mice, WT and IRE1a deficient mice untreated or injected with tunicamycin, and XBP1 deficient mice injected with luciferase or IRE1a siRNA.
2012-10-17 | E-GEOD-40515 | biostudies-arrayexpress
Project description:The ER-resident protein kinase/endoribonuclease IRE1 is activated through trans-autophosphorylation in response to protein folding overload in the ER lumen and maintains ER homeostasis by triggering a key branch of the unfolded protein response. Here we show that mammalian IRE1a in liver cells is also phosphorylated by a kinase other than itself in response to metabolic stimuli. Glucagon stimulated protein kinase PKA, which in turn phosphorylated IRE1a at Ser724, a highly conserved site within the kinase activation domain. Blocking Ser724 phosphorylation impaired the ability of IRE1a to augment the upregulation by glucagon signaling of the expression of gluconeogenic genes. Moreover, hepatic IRE1a was highly phosphorylated at Ser724 by PKA in mice with obesity, and silencing hepatic IRE1a markedly reduced hyperglycemia and glucose intolerance. Hence, these results suggest that IRE1a integrates signals from both the ER lumen and the cytoplasm in the liver and is coupled to the glucagon signaling in the regulation of glucose metabolism. We used DNA microarray to analyze the transcriptomic change upon IRE1a overexpression or IRE1a depletion in primary hepatocytes, to study the changes related to IRE1a Primary hepatocytes were infected with the desired adenoviruses (Ad-EGFP, Ad-WT, Ad-S724A, Ad-shCON, Ad-shIRE1a#2) or treated with glucagon. Total cellular RNA was isolated with TRIzol (Invitrogen) and subjected to analysis by Affymetrix Mouse Genome 430 2.0 Arrays. Three experiments were independently conducted.
2011-08-30 | E-GEOD-31638 | biostudies-arrayexpress
Project description:The ER-resident protein kinase/endoribonuclease IRE1 is activated through trans-autophosphorylation in response to protein folding overload in the ER lumen and maintains ER homeostasis by triggering a key branch of the unfolded protein response. Here we show that mammalian IRE1a in liver cells is also phosphorylated by a kinase other than itself in response to metabolic stimuli. Glucagon stimulated protein kinase PKA, which in turn phosphorylated IRE1a at Ser724, a highly conserved site within the kinase activation domain. Blocking Ser724 phosphorylation impaired the ability of IRE1a to augment the upregulation by glucagon signaling of the expression of gluconeogenic genes. Moreover, hepatic IRE1a was highly phosphorylated at Ser724 by PKA in mice with obesity, and silencing hepatic IRE1a markedly reduced hyperglycemia and glucose intolerance. Hence, these results suggest that IRE1a integrates signals from both the ER lumen and the cytoplasm in the liver and is coupled to the glucagon signaling in the regulation of glucose metabolism. We used DNA microarray to analyze the transcriptomic change upon IRE1a overexpression or IRE1a depletion in primary hepatocytes, to study the changes related to IRE1a
2011-08-31 | GSE31638 | GEO
Project description:IRE1a and XBP1 are key regulators of the unfolded protein response (UPR). XBP1 ablation causes profound hypolipidemia in mice, and triggers feedback activation of its upstream enzyme IRE1a, instigating regulated IRE1-dependent decay (RIDD), an mRNA degradation mechanism dependent on IRE1a's endoribonuclease activity. Comprehensive microarray analysis of XBP1 and/or IRE1a deficient liver identified genes involved in lipogenesis and lipoprotein metabolism as RIDD substrates, which might contribute to the suppression of plasma lipid levels by activated IRE1a.
2012-10-17 | GSE40515 | GEO
Project description:The purpose of the study was to examine the role of the IRE1a-XBP1 pathway during Th2 lymphocyte activation and differentiation. In vitro Th2 cells were treated with 4μ8c, a drug that specifically inhibits IRE1a endonuclease activity, and transcriptomes were compared.
2018-07-20 | E-MTAB-6894 | biostudies-arrayexpress
Project description:IRE1a is a critical modulator of the unfolded protein response. Its RNAse activity generates the mature transcript for the XBP1 transcription factor and also degrades other ER associated mRNAs in a process termed Regulated IRE1a Dependent mRNA Decay or RIDD. To determine if IRE1a is critical in the response to oncogenic Ras we used ShRNA to knockdown Ire1a or Xbp1 in primary mouse epidermal keratinocytes transduced with a v-HRAS retrovirus.
2017-06-01 | GSE70899 | GEO
Project description:BLI tightly controls the protein kinase activity of IRE1A in plants,and IRE1A plays new roles in plant growth and development
2019-11-01 | GSE124235 | GEO
Project description:We conducted RNA-seq and Ribo-seq for the same samples. IRE1a was knockde down by siRNA. There are two replicates for each group.
2023-12-31 | GSE199948 | GEO
Project description:GL261-derived glioblastoma stem cells (GSCs) form aggressive tumors when implanted into the brains of C57BL/6 mice. We used spatial transcriptomics to analyze brain sections of tumor-bearing C57BL/6 mice at 28 days post-implantation
2024-03-28 | GSE245263 | GEO