Unfolded Protein Response
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE3130 | GEO | 2005/08/16
SECONDARY ACCESSION(S): PRJNA93029
REPOSITORIES: GEO
Similar Datasets
Project description:To dissect the requirements of membrane protein degradation from the ER, we expressed the mouse major histocompatibility complex class I heavy chain H-2K(b) in yeast. Like other proteins degraded from the ER, unassembled H-2K(b) heavy chains are not transported to the Golgi but are degraded in a proteasome-dependent manner. The overexpression of H-2K(b) heavy chains induces the unfolded protein response (UPR). In yeast mutants unable to mount the UPR, H-2K(b) heavy chains are greatly stabilized. This defect in degradation is suppressed by the expression of the active form of Hac1p, the transcription factor that upregulates UPR-induced genes. These results indicate that induction of the UPR is required for the degradation of protein substrates from the ER.
2005-06-28 | E-SMDB-1576 | biostudies-arrayexpress
Project description:To dissect the requirements of membrane protein degradation from the ER, we expressed the mouse major histocompatibility complex class I heavy chain H-2K(b) in yeast. Like other proteins degraded from the ER, unassembled H-2K(b) heavy chains are not transported to the Golgi but are degraded in a proteasome-dependent manner. The overexpression of H-2K(b) heavy chains induces the unfolded protein response (UPR). In yeast mutants unable to mount the UPR, H-2K(b) heavy chains are greatly stabilized. This defect in degradation is suppressed by the expression of the active form of Hac1p, the transcription factor that upregulates UPR-induced genes. These results indicate that induction of the UPR is required for the degradation of protein substrates from the ER. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed
2005-08-16 | E-GEOD-3130 | biostudies-arrayexpress
Project description:The unfolded protein response (UPR) couples cellular translation rates and gene expression to the protein folding status of the endoplasmic reticulum (ER). Upon activation, the UPR machinery elicits a general suppression of protein synthesis and activation of stress gene expression, which act coordinately to restore protein folding homeostasis. We report here that UPR activation promotes the release of signal sequence-encoding mRNAs from the ER to the cytosol as a mechanism to decrease protein influx into the ER. This release of mRNA begins rapidly, then gradually recovers with ongoing stress. Upon release into the cytosol, these mRNAs have divergent fates: some synthesize full-length proteins, while others are translationally inactive and retain nascent protein chains. Together, these findings identify the dynamic subcellular localization of mRNAs and translation as a regulatory feature of the cellular response to protein folding stress. Cells were treated with a timecourse of Thapsigargin or DTT, then fractionated and analyzed by mRNA-seq or ribosome profiling
2014-08-28 | E-GEOD-53743 | biostudies-arrayexpress
Project description:Homeostatic control mechanisms are essentil to life. One such mechanism, the unfolded protein response (UPR) operates in all eukarytic cells to adjust protein folding capacity of the endoplasmic reticulum (ER) according to need. UPR induction in all eurkarytic cells to date involves Ire1 (kinase/endonuclease transmembrane protein) mediated a non-convential splicing of Hac1/XBP1 mRNA, encoding for a potent transcription factor. UPR induction causes a comprehensive transcriptional upregulation of the folding capacity in the ER. Here we studied the global transcriptional profile of the UPR in fission yeast. Fission yeast lacks a clear homolog of Hac1/XBP1. Instead Ire1 maintains ER homeostasis through two post-transciptional programs: selective mRNA decay and processing of Bip1 mRNA (encoding for a major HS70-familiy member in the ER) thereby stabilizing it.
2012-11-21 | GSE40298 | GEO
Project description:The unfolded protein response (UPR) couples cellular translation rates and gene expression to the protein folding status of the endoplasmic reticulum (ER). Upon activation, the UPR machinery elicits a general suppression of protein synthesis and activation of stress gene expression, which act coordinately to restore protein folding homeostasis. We report here that UPR activation promotes the release of signal sequence-encoding mRNAs from the ER to the cytosol as a mechanism to decrease protein influx into the ER. This release of mRNA begins rapidly, then gradually recovers with ongoing stress. Upon release into the cytosol, these mRNAs have divergent fates: some synthesize full-length proteins, while others are translationally inactive and retain nascent protein chains. Together, these findings identify the dynamic subcellular localization of mRNAs and translation as a regulatory feature of the cellular response to protein folding stress.
2014-08-28 | GSE53743 | GEO
Project description:Membrane integrity at the endoplasmic reticulum (ER) is tightly regulated and its disturbance is implicated in metabolic diseases. Using an engineered sensor that activates the unfolded protein response (UPR) exclusively when normal ER membrane lipid composition is compromised, we identified pathways beyond lipid metabolism that are necessary to maintain ER integrity in yeast and in C. elegans. To systematically validate yeast mutants that disrupt ER membrane homeostasis, we identified a lipid bilayer stress (LBS) sensor in the UPR transducer protein Ire1, located at the interface of the amphipathic and transmembrane helices. Furthermore, transcriptome and chromatin immunoprecipitation (ChIP) analyses pinpoint the UPR as a broad-spectrum compensatory response wherein LBS and proteotoxic stress deploy divergent transcriptional UPR programs. Together, these findings reveal the UPR program as the sum of two independent stress responses, an insight that could be exploited for future therapeutic intervention.
2020-04-24 | GSE131146 | GEO
Project description:The accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) causes stress and induces the unfolded protein response (UPR) which is characterised in part by the transcriptional induction of genes involved in assisting protein folding. Translational responses to ER stress have been less well described and here we report on a genome-wide analysis of translational regulation in the response to the ER stress-inducing agent dithiothreitol (DTT) in Saccharomyces cerevisiae. Although the observed polysome profiles were similar under control and ER stress conditions microarray analysis identified transcipt-specific translational regulation. Genes with functions in ribosomal biogenesis and assembly were translationally repressed under ER stress. In contrast mRNAs for known UPR genes, including the UPR transcription factor HAC1, the ER-oxidoreductase ERO1 and the ER-associated protein degradation (ERAD) gene DER1 were enriched in polysomal fractions under ER stress conditions. In addition, we show that splicing of HAC1 mRNA is required for efficient ribosomal loading and that Gcn2p is required for normal HAC1 splicing, so shedding light on the role of this protein kinase in the UPR pathway. Experiment Overall Design: Polyribosomes were extracted from S. cerevisiae cells treated with 2 mM DTT or water (control), and fractionated according to ribosome loading. Following RNA purification from these fractions, for each sub-polysomal and polysomal RNA sample, fractions from three independent extracts per treatment (DTT/control) were pooled.
2008-06-11 | E-GEOD-10091 | biostudies-arrayexpress
Project description:The unfolded protein response (UPR) continually monitors the protein folding capacity of the endoplasmic reticulum (ER). In S. pombe, Ire1, an ER membrane-resident kinase/endoribonuclease, utilizes a mechanism of selective degradation of ER-targeted mRNAs (RIDD) to maintain ER homeostasis. Here, we used a genetic screen to identify factors critical to the Ire1-mediated UPR response in S. pombe and found several proteins, Dom34, Hbs1 and SkiX, previously implicated in ribosome rescue and the no-go-decay (NGD) pathway. Ribosome profiling in ER-stressed cells lacking these factors revealed that Ire1-mediated cleavage on ER-associated mRNAs results in ribosome stalling on the cleaved transcript and, ultimately in full mRNA degradation. The process engages mechanisms of precise, iterated cleavage of the mRNAs and ribosome rescue. This clear signature allowed us to discover hundreds of novel mRNA targets of Ire1. Our results reveal that the UPR in S. pombe executes RIDD in an intricate interplay between Ire1, translation, and the NGD surveillance pathway, and establish a critical role for NGD in maintaining ER homeostasis.
2017-09-14 | GSE98934 | GEO
Project description:The ARV1-encoded protein mediates sterol transport from the endoplasmic reticulum (ER) to the plasma membrane. Yeast ARV1 mutants accumulate multiple lipids in the ER and are sensitive to pharmacological modulators of both sterol and sphingolipid metabolism. Using fluorescent and electron microscopy, we demonstrate sterol accumulation, subcellular membrane expansion, elevated lipid droplet formation and vacuolar fragmentation in ARV1 mutants. Motif-based regression analysis of ARV1 deletion transcription profiles indicates activation of Hac1p, an integral component of the UPR. Accordingly, we show constitutive splicing of HAC1 transcripts, induction of a UPR reporter and elevated expression of UPR targets in ARV1 mutants. IRE1, encoding the unfolded protein sensor in the ER lumen, exhibits a lethal genetic interaction with ARV1, indicating a viability requirement for the UPR in cells lacking ARV1. Surprisingly, ARV1 mutants expressing a variant of Ire1p defective in sensing unfolded proteins are viable. Moreover these strains also exhibit constitutive HAC1 splicing that interacts with DTT-mediated perturbation of protein folding. These data suggest a component of UPR induction in arv1? strains is distinct from protein misfolding. Decreased ARV1 expression in murine macrophages also results in UPR induction, particularly up-regulation of activating transcription factor-4, C/EBP homologous protein (CHOP) and apoptosis. Cholesterol loading or inhibition of cholesterol esterification further elevated CHOP expression in ARV1 knockdown cells. Thus, loss or down-regulation of ARV1 disturbs membrane and lipid homeostasis resulting in a disruption of ER integrity, one consequence of which is induction of the UPR. Yeast strains were grown to mid-logarithmic stage (A600=0.5-0.6) for RNA extraction and hybridization on Ye6100 or S98 Affymetrix gene chips. The control array (sample name C) was carried out in duplicate. The ARV1 mutant array (sample name A) was carried out in triplicate. Both ARV1 mutants Ye6100 arrays were compared to the same control Ye6100 array. Strains represent different isolates of the same genotype, mating type and genetic background (w303). Sturley lab collection (SCY) strains include SCY328 and SCY2004 for controls and SCY820 and SCY840 for ARV1 mutants.
2011-02-17 | E-GEOD-26801 | biostudies-arrayexpress
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