Genome-wide binding targets of GBF2 in ER stress
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ABSTRACT:
ORGANISM(S): Arabidopsis thaliana
PROVIDER: GSE197790 | GEO | 2023/02/01
REPOSITORIES: GEO
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Project description:Sse1, yeast cytosolic Hsp110 chaperone, is a wellknown Nucleotide Exchange Factor (NEF), a protein-disaggregase and a Chaperone linked to Protein Synthesis (CLIPS). Here we demonstrate SSE1’s genetic interaction with IRE1 and HAC1, the Endoplasmic Reticulum-Unfolded Protein Response (ER-UPR) sensors. sse1Δ strain exhibits an ER-UPR signalling-dependent resistance to tunicamycin-induced ER stress. Importantly, ER-stress-responsive reorganization of translating ribosomes from polysomes to monosomes is inefficient in SSE1 deleted strain leading to uninterrupted protein translation and starkly different ER-UPR kinetics. sse1Δ exhibits faster ER-UPR induction and quicker reversal to basal state compared to wildtype (WT) cells. Interestingly, ER-stress mediated yeast cell division arrest is escaped in sse1Δ strain during long term tunicamycin stress indicating important role of this chaperone in controlling cell division during ER stress. Furthermore, sse1Δ strain shows significantly higher cell viability in comparison to WT yeast, following short-term as well as long-term tunicamycin stress. In summary, we show that cytosolic chaperone Sse1 genetically interacts with ER-UPR pathway, controls the kinetics of ER-UPR, stress-induced cell division arrest and cell viability during global ER stress by tunicamycin.
2024-04-19 | PXD045382 | Pride
Project description:Chronic endoplasmic reticulum (ER) stress results in toxicity that contributes to multiple human disorders. We report a stress resolution pathway initiated by the nuclear receptor LRH-1 that is independent of known unfolded protein response (UPR) pathways. Like mice lacking primary UPR components, hepatic Lrh-1-null mice cannot resolve ER stress, despite a functional UPR. In response to ER stress, LRH-1 induces expression of the kinase Plk3, which phosphorylates and activates the transcription factor ATF2. Plk3-null mice also cannot resolve ER stress, and restoring Plk3 expression in Lrh-1-null cells rescues ER stress resolution. Reduced or heightened ATF2 activity also sensitizes or desensitizes cells to ER stress, respectively. LRH-1 agonist treatment increases ER stress resistance and decreases cell death. We conclude that LRH-1 initiates a novel pathway of ER stress resolution that is independent of the UPR, yet equivalently required. Targeting LRH-1 may be beneficial in human disorders associated with chronic ER stress. 24 total samples. One sample represents one mouse. Three samples were analyzed from the following groups: Lrh-1 f/f (control littermates) treated with vehicle, Lrh-1 f/f treated with tunicamycin (TM; 1mg/kg BW for 24h), Lrh-1 f/f treated with tunicamycin and DLPC (100mg/kg BW 4x), Lrh-1 f/f treated with tunicamycin and vehicle for DLPC, Lrh-1 liver-specific KO mice (LKO) treated with vehicle, Lrh-1 LKO treated with tunicamycin, and Lrh-1 LKO treated with tunicamycin and DLPC, Lrh-1 LKO treated with tunicamycin and vehicle for DLPC
2015-05-12 | E-GEOD-68718 | biostudies-arrayexpress
Project description:We tracked the gene expression events following treatment of maize seedlings with the endoplasmic reticulum (ER) stress agent tunicamycin. ER stress elicits the unfolded protein response (UPR) and when plants are faced with persistent stress, the UPR transitions from an adaptive or cell survival phase to programmed cell death.
2018-05-30 | GSE111250 | GEO
Project description:eIF2α phosphorylation-mediated translational regulation is crucial for global translation repression by various stresses, including the unfolded protein response (UPR). However, translational control during UPR has not been demonstrated in yeast. This study investigated ribosome ubiquitination-mediated translational controls during UPR. Tunicamycin-induced ER stress enhanced the levels of ubiquitination of the ribosomal proteins uS10, uS3 and eS7. Not4-mediated monoubiquitination of eS7A was required for resistance to tunicamycin, whereas E3 ligase Hel2-mediated ubiquitination of uS10 was not. Ribosome profiling showed that the monoubiquitination of eS7A was crucial for translational regulation, including the upregulation of the spliced form of HAC1 (HAC1i) mRNA and the downregulation of Histidine triad NucleoTide-binding 1 (HNT1) mRNA. Downregulation of the deubiquitinating enzyme complex Upb3-Bre5 increased the levels of ubiquitinated eS7A during UPR in an Ire1-independent manner. These findings suggest that the monoubiquitination of ribosomal protein eS7A plays a crucial role in translational controls during the ER stress response in yeast.
2020-11-12 | GSE128578 | GEO
Project description:The perturbations of ER homeostasis lead to the development of a condition referred to as ER stress. However, the repressive trimethylation on histone H3 lysine 27 (H3k27me3) under ER stress remains largely elusive. Here, we identify a critical role for H3k27me3 to impact the expression of Crytochrome 1 (Cry1). To examine the effect of ER stress on histone modification, MEFs were treated with vehicle 2μg/ml tunicamycin for 6 h. The cell lysate were collected and ChIP-seq assays were performed with the primary H3k27me3 or H3k4me3 antibody. When compared to the Vehicle group, the tunicamycin treatment reduced the 23,008 H3k27me3 peaks. In line with the roles of H3k27me3 in the regulation of gene transcriptions, annotation of the peak in genomic positions to the cloest genes indicated that many peaks were positioned after the transcription start site. Cry1 is one of the most regulated genes. However, the tunicamycin treatment slightly reduced H3k4me3 modification in MEFs. There are only 3109 peaks were decreased by the tunicamycin treatment. These data suggest ER stress selectively regulated H3k27me3 modification in the hisone 3 and reactivate Cry1 gene expression in MEFs.
2021-05-01 | GSE131068 | GEO
Project description:The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) results in the condition called âER stressâ which induces the unfolded protein response (UPR) which is a complex cellular process that includes changes in expression of many genes. Failure to restore homeostasis in the ER is associated with human diseases. To identify the underlying changes in gene expression in response to ER stress, we induced ER stress in human B-cells and then measured gene expression at 10 time-points. We followed up those results by studying cells from 60 unrelated people. We rediscovered genes that were known to play a role in ER stress response and uncovered several thousand genes that are not known to be involved. Two of these are VLDLR and INHBE which showed significant increase in expression following ER stress in B-cells and in primary fibroblasts. To study the links between unfolded protein response and disease susceptibility, we identified ER stress responsive genes that are associated with human diseases and assessed individual differences in ER stress response. Many of the UPR genes are associated with Mendelian disorders such as Wolfram syndrome and complex human diseases including amyotrophic lateral sclerosis and diabetes. Data from two independent samples showed extensive individual variability in ER stress response. Additional analyses with monozygotic twins revealed significant correlations within twin pairs in their responses to ER stress thus showing evidence for heritable variation among individuals. These results have implications for basic understanding of ER function and its role in disease susceptibility. Keywords: array-based gene expression We measured gene expression levels in immortalized B cells from members of 60 unrelated CEPH-Utah grandparents. Each individual was treated for 8 hours with either DMSO or with 4 ug/ml of tunicamycin. Gene expression was measured to identify tunicamycin-responsive genes. To assess whether there is a genetic component to the individual variation in gene expression response to ER stress, we used microarrays to measure expression of genes in 26 monozygotic twin pairs treated with either DMSO or 500 nM thapsigargin for 4 hours.
2010-04-08 | E-GEOD-19519 | biostudies-arrayexpress
Project description:ER stress and the unfolded protein response (UPR) involve extensive proteome remodeling in many cell compartments. However, a comprehensive analysis has been lagging due to technological limitations. Here we employ SILAC-based proteomics to quantify over 6,200 proteins at increasing concentrations of tunicamycin in HeLa cells. We further compare the effects of tunicamycin to those of thapsigargin and DTT, both activating the UPR through different mechanisms. The systematic description of the proteome-wide expression changes following proteostatic stress is a resource for the scientific community, which enables to discover novel players involved the pathophysiology of disorders linked to proteostasis. Here, we identified 38 proteins, not previously linked to the UPR, whose expression increases, of which 15 would likely remediate ER stress, and the remainder may contribute to pathological outcomes. Unexpectedly, we see few strongly downregulated proteins, despite expression of the pro-apoptotic transcription factor CHOP, suggesting that IRE1-dependent mRNA decay (RIDD) has a limited contribution to ER-stress mediated cell death in our system.
2019-11-01 | PXD013496 | Pride
Project description:Virus infection and over expression of protein in cytosol induce a subset of HSP70s. We named this response the Cytosolic Protein Response (CPR) and have been investigating it in the context of a parallel mechanism in the soluble cytosol with the UPR, and as a subcomponent of the larger HS response. This experiment was carried out to study the transcriptional aspect of CPR. In this analysis, we have triggered CPR by infiltrating proline analogue, L-azetidine-2-carboxylic acid (AZC) into Arabidopsis mature leaves. Since AZC trigger unfolded protein response(UPR) in ER as well as CPR, we have included tunicamycin treatment, which is a specific inducer of UPR to subtract the effect of UPR from the AZC response. Heat shocked samples were included to identify CPR as a subcomponent of larger HS response. We used microarray data to identify the genes upregurated by CPR. These genes were commonly upregulated by AZC and HS but not by tunicamycin treatment. Experiment Overall Design: Arabidopsis mature leaves were infiltrated with AZC or L-Proline (control of AZC) and tunicamycin or DMF(solvent control of tunicamycin). For the heat shock treatment, six mature leaves were detached from plant and incubated at 37 °C or 20°C (as a control) for a period of 1h. The experiment was repeated three times for AZC and HS treatment (3 biological replication). Tunicamycin experiment was repeated five times due to large valiation in the responses (5 biological replication).
2009-01-13 | E-GEOD-11758 | biostudies-arrayexpress
Project description:GPT inhibitor Tunicamycin develops ER stress causing anti-angiogenic response in breast tumor microvasculature due to unfolded protein response-mediated apoptosis. cDNA microarray identified 123 and 454 differentially regulated genes with 10 genes overlapping between 3h and 32 h of Tunicamycin treatment. Alg-2 expression is inconsistent but not the Dpms. Evidences support that Tunicamycin completely destroys DPMS activity in capillary endothelial cells without affecting its protein or the mRNA levels but by knocking down the phosphorylation. DPMS’ contribution to developing upr during ER stress has therefore been evaluated because of its inherent regulatory property of GPT. FTIR spectroscopy confirmed protein denaturation. Restablishing the phosphorylation status helps the DPMS regaining its activity. As a result, ER stress is reduced reversing apoptosis and bringing more cells into cycling with normal cellular morphology. Furthermore, differential expression of DPMS in breast tumor microvasculature during Tunicamycin therapy raises its potential as a tumor prognostic marker in the clinic.
2017-11-15 | GSE33729 | GEO
Project description:Objective: Induction of ER stress has been shown to promote NP cell apoptosis and disc degeneration. However, little is known about its regulation by hypoxia and its contribution to extracellular matrix homeostasis. Methods: NP cells were culture under hypoxia (1% O2) and normoxia (21% O2) to assess ER stress status. Tunicamycin and thapsigargin were used to induce canonical ER stress pathways and effects on cell secretome were assessed by proteomic analysis using mass spectrometry. The relevance of these findings to aging and degeneration was investigated by analyzing microarray data of NP tissues from aged mice (GSE134955) and degenerated human discs (GSE70362). Results: NP cells exhibited lower ER stress levels under hypoxia. ER stress inducers tunicamycin and thapsigargin promoted a canonical unfolded protein response. UPR further induced HIF-1 activity under hypoxia. NP cell secretome under ER stress showed an increased secretory pathway with a concomitant decrease in collagens, HAPLN1, and cell adhesion related proteins. Similar to our cell culture studies, NP tissues from aged mice and degenerated human discs presented higher levels of UPR markers and decreased levels of matrix components.
2020-12-03 | PXD019151 | Pride