Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Overexpression of SSZ1 suppresses temperature sensitivity phenotype of yeasts indicating its novel function to maintain cellular robustness

ABSTRACT: Ssz1p plays multifunctional roles in diverse cellular activities including forming a ribosome-associated complex to assist new protein synthesis and activating pleiotropic drug resistance (PDR) pathway. Here we report a novel function of SSZ1 to maintain cellular robustness when it is overexpressed. We found overexpression of SSZ1 can suppress the death phenotype of the double mutant Δire1Δscj1 and the temperature sensitivity (TS) phenotype of scj1-1Δire1. Microarray analyses showed that overexpression of SSZ1 induced up-regulation of the genes involved in the PDR pathway and the cell wall integrity (CWI) pathway, but not the unfolded protein response (UPR) pathway. However, overexpression of PDR1 and PDR5 cannot significantly suppress the TS phenotype of scj1-1Δire1, and overexpression of SSZ1 cannot up-regulate the gene expression of lacZ under the control of the unfolded protein response element in SSZ1OEΔire1 compared with that in Δire1. We infer that the suppression is not through the PDR pathway or through the UPR pathway. It may be through regulating downstream genes of the CWI pathway. Moreover, the peptide-binding domain of Ssz1p is necessary for its suppression of TS phenotype of scj1-1Δire1.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE75557 | GEO | 2016/12/01

SECONDARY ACCESSION(S): PRJNA304591

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Proteomic response of yeast cells to 2-deoxyglucose exposure (0.2%, 2.5h)

Project description:Cancer cells display an altered metabolism with increased glycolysis and glucose uptake. Anti-cancer strategies targeting glycolysis through metabolic inhibitors have been considered. The glucose analog 2-deoxyglucose (2DG) is imported into cells and after phosphorylation becomes 2DG-6-phosphate, a toxic by-product that inhibits glycolysis. 2DG has other cellular effects and can induce resistance. Using yeast as a model, we performed an unbiased, mass-spectrometry-based approach to probe the cellular effects of 2DG on the proteome and study resistance mechanisms. We found that two 2DG-6-phosphate phosphatases, Dog1 and Dog2, were induced upon exposure to 2DG and participated in 2DG detoxication. 2DG induced Dog2 by activating several signaling pathways, such as the MAPK (the p38 ortholog Hog1)-based stress-responsive pathway, the unfolded protein response (UPR) triggered by 2DG-induced ER stress, and the MAPK (Slt2)-based cell wall integrity (CWI) pathway. Thus, 2DG-induced interference with cellular signaling rewired the expression of these endogenous phosphatases to promote 2DG resistance. Consequently, loss of the UPR or CWI pathways led to 2DG hypersensitivity. In contrast, DOG2 was transcriptionally repressed by glucose availability through the inhibition of the Snf1/AMPK pathway, and glucose-repression mutants were 2DG-resistant. The characterization and genome resequencing of spontaneous 2DG-resistant mutants revealed that DOG2 overexpression was a common strategy to achieve 2DG resistance. A human Dog2 homolog, HDHD1, also displays 2DG-6-phosphate phosphatase activity in vitro, and its overexpression conferred 2DG resistance in HeLa cells, suggesting potential interference with chemotherapies involving 2DG.

2019-09-09 | PXD014373 | Pride

Nuclear receptor LRH-1/NR5A2 is required and targetable for liver endoplasmic reticulum stress resolution

2015-05-12 | GSE68718 | GEO

Nuclear receptor LRH-1/NR5A2 is required and targetable for liver endoplasmic reticulum stress resolution.

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

Microarray expression data of HT-29 cells treated with spautin-1 or buformin under 2DG- or tunicamycin-stressed conditions

Project description:Spautin-1 as well as buformin showed preferential cytotoxicity under 2-deoxy-D-glucose (2DG)-stressed, but not tunicamycin-stressed conditions in HT-29 cells. By a microarray-based transcription analyses, we previously identified an unfolded protein response (UPR) expression signature, consisting of 246 probes up- or down-regulated in glucose starvation- and 2DG-stressed HT-29 and other cancer cell lines. Thus, we compared the effects of spautin-1 and buformin on the UPR transcriptional program. The two UPR inhibitors partly canceled 2DG-induced, but not TM-induced changes in UPR expression signature, indicating that spautin-1 can indeed suppress the UPR transcriptional program under 2DG-stressed conditions.

2022-07-07 | GSE189850 | GEO

Transcription profiling of yeast expressing mouse major histocompatibility complex class I heavy chain H-2K(b)

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

Unfolded Protein Response

2005-08-16 | E-GEOD-3130 | biostudies-arrayexpress

Whole transcriptome profiles and ribosome profiling of thapsigargin- and tunicamycin-treated LN308 cells

Project description:Accumulation of unfolded proteins in the endoplasmic reticulum triggers the unfolded protein response (UPR), an adaptive signal transduction pathway aimed at reinstating cellular homeostasis, or, if that fails, at triggering of apoptosis. To gain a comprehensive and systems-wide understanding of the UPR, we have pursued a multi-omics approach that, upon chemical induction of the UPR with two different compounds, monitors in parallel several parameters in the astrocytoma cell line LN-308. Changes to the cellular transcriptome (by high throughput sequencing) and altered translation status (by ribosome profiling) were measured after 2h and 6h of treatment.

2020-04-30 | GSE129757 | GEO

Transgenerational inheritance of mitochondrial stress adaptation in C. elegans

Project description:Using Caenorhabditis elegans to investigate environmental cues-induced mitochondrial dysfunction, we found that exposure to electron transport chain (ETC) inhibitors at the parental generation initiates the transmission of heritable information to descendants and make descendants stress-adaptive. This mitochondrial stress adaptation phenotype can persist for at least three generations. Animals lacking histone H3K4me3 chromatin modifiers, or the methyltransferase of N6-methyldeoxyadenosine (6mA), lose the ability to initiate stress adaptation in progeny. H3K4me3 plays a role upstream of 6mA, while both mark promoter regions of mitochondrial unfolded protein response (UPR mt ) genes and activate the UPR mt pathway to alleviate mitochondrial damage.

2017-07-26 | GSE85835 | GEO

SARS-CoV-2 ORF8 interactome in the secretory pathway

Project description:The replication machinery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is closely associated with the endoplasmic reticulum (ER) in host cells. Activation of the unfolded protein response (UPR) is a strategy hijacked by coronavirus to facilitate its replication and suppress host innate immunity. Here, we identified that many protein disulfide isomerase family members are enriched in the ORF8 interactome, and found that ORF8 protein accumulates in the ER and escapes the degradation system by forming mixed disulfide complexes with ER oxidoreductases. ORF8 induces the activation of three UPR pathways through targeting key UPR components, remodels ER morphology and accelerates protein trafficking.

2022-08-12 | PXD032035 | Pride

ATF6 promotes colorectal cancer growth and stemness by regulating the Wnt pathway

Project description:The unfolded protein response (UPR) maintains endoplasmic reticulum (ER) homeostasis by sensing protein-folding stress and orchestrating cellular adaptation via the ER-transmembrane proteins IRE1, PERK and ATF6. Malignant cells can co-opt UPR signaling by IRE1 and PERK to sustain tumor growth; however, the importance of ATF6 in cancer remains poorly deciphered. We observed elevated ATF6 transcriptional activity in several cancers including colorectal carcinoma (CRC). Genetic silencing or small molecule inhibition of ATF6 blocked cell cycle progression and reduced viability of several human CRC cell lines in vitro and disrupted tumor progression in vivo. Unexpectedly, ATF6 interference also disabled Myc and Wnt signaling and reduced stemness. ATF6 inhibition attenuated growth of organoids derived from malignant but not normal human intestinal tissue, reducing Wnt-pathway activity and driving cellular differentiation. Wnt-surrogate agonism rescued the growth inhibitory phenotype of ATF6 interference. Our findings identify ATF6 as an unexpected facilitator of oncogenic Wnt signaling in CRC.

2024-08-12 | MSV000095581 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data