Oxidative quality control regulates response to ER stress through translation control
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE68006 | GEO | 2016/05/31
SECONDARY ACCESSION(S): PRJNA281482
REPOSITORIES: GEO
Similar Datasets
Project description:The transcriptomic response after 3 hours of DTT treatment shows there is not a drastic difference in most genes between WT and skn7â, yap1â . Vma13â, sse2â were also used as part of the study. Organism : Saccharomyces cerevisiae, Agilent Yeast Gene expression 8x15K Array AMADID: 016322
2016-05-31 | E-GEOD-68006 | biostudies-arrayexpress
Project description:Transcriptional profiling of ER stress condition comparing control (untreated), dithiothreitol (DTT) treated, or tunicamycin (TM) treated conditions on P. angusta DL1 strain.
2015-07-22 | GSE68528 | GEO
Project description:Transcriptional profiling of Control and hac1 deletion mutant in ER stress condition on P. angusta DL1 strain. WT+ER stress vs. hac1 deletion mutant+ER stress. Six-condition experiment: Control+ER stress (TM 30, 60, 120min; DTT 30, 60, 120min) vs. hac1 deletion mutant+ER stress condition (TM 30, 60, 120min; DTT 30, 60, 120min) in P. angusta DL1 strain. Independently grown and harvested. Dye-swapping.
2015-07-22 | E-GEOD-68217 | biostudies-arrayexpress
Project description:Fcp1 is a protein phosphatase that facilitates transcription elongation and termination by dephosphorylating the C-terminal domain of RNA Polymerase II. Here, we report an unanticipated role in the repression of the oxidative stress induced genes. High-throughput genetic and gene expression profiling of FCP1 mutants uncovered a link to Skn7, a key transcription factor in the oxidative stress response pathways, as well as a link to the Mediator complex kinase subunit, Cdk8. Interestingly, loss of CDK8 suppressed FCP1 mutant growth phenotypes upon exposure to oxidative stress, an effect dependent on SKN7. Furthermore, FCP1 and CDK8 regulated Skn7 protein levels and stability, as well as the expression of target genes through interdependent mechanisms. Focusing on the latter, while the FCP1 mutant robustly increased mRNA levels of Skn7-dependent genes under basal and induced conditions, it decreased Skn7 promoter occupancy, both defects normalized by loss of CDK8. Intriguingly, both FCP1 and CDK8 also altered Skn7 phosphorylation levels, a modification known to control Skn7 function, although the significance of this effect and residues involved remain unclear. Loss of CDK8 also alleviated the sensitivity of FCP1 mutants to other stressors, implicating these factors in regulating the response to other environmental insults.
2019-09-10 | GSE128936 | GEO
Project description:Transcriptional profiling of ER stress condition comparing control (untreated), dithiothreitol (DTT) treated, or tunicamycin (TM) treated conditions on P. angusta DL1 strain. Six-condition experiment: normal condition vs. ER stress condition (TM 30, 60, 120min; DTT 30, 60, 120min) in P. angusta DL1 strain. Independently grown and harvested. Two replicates per array.
2015-07-22 | E-GEOD-68528 | biostudies-arrayexpress
Project description:The endoplasmic-reticulum quality-control (ERQC) system shuttles misfolded proteins for degradation by the proteasome through the well-defined ER-associated degradation (ERAD) pathway. In contrast, very little is known about the role of autophagy in ERQC. Macro-autophagy, a collection of pathways that deliver proteins through autophagosomes (APs) for degradation in the lysosome (vacuole in yeast), is mediated by autophagy-specific proteins, Atgs, and regulated by Ypt/Rab GTPases. Until recently, the term ER-phagy was used to describe degradation of ER membrane and proteins in the lysosome under stress: either ER stress induced by drugs or whole-cell stress induced by starvation. These two types of stresses induce micro-ER-phagy, which does not use autophagic organelles and machinery, and non-selective autophagy. Here, we characterize the macro-ER-phagy pathway and uncover its role in ERQC. This pathway delivers 20-50% of certain ER-resident membrane proteins to the vacuole and is further induced to >90% by overexpression of a single integral-membrane protein. Even though such overexpression in cells defective in macro-ER-phagy induces the unfolded-protein response (UPR), UPR is not needed for macro-ER-phagy. We show that macro-ER-phagy is dependent on Atgs and Ypt GTPases and its cargo passes through APs. Moreover, for the first time the role of Atg9, the only integral-membrane core Atg, is uncoupled from that of other core Atgs. Finally, three sequential steps of this pathway are delineated: Atg9-dependent exit from the ER en route to autophagy, Ypt1- and core Atgs-mediated pre-autophagsomal-structure organization, and Ypt51-mediated delivery of APs to the vacuole.
| S-EPMC4504476 | biostudies-literature
Project description:Endoplasmic reticulum (ER) quality control mechanisms target terminally misfolded proteins for ER-associated degradation (ERAD). Misfolded glycophosphatidylinositol-anchored proteins (GPI-APs) are, however, generally poor ERAD substrates and are targeted mainly to the vacuole/lysosome for degradation, leading to predictions that a GPI anchor sterically obstructs ERAD. Here we analyzed the degradation of the misfolded GPI-AP Gas1* in yeast. We could efficiently route Gas1* to Hrd1-dependent ERAD and provide evidence that it contains a GPI anchor, ruling out that a GPI anchor obstructs ERAD. Instead, we show that the normally decreased susceptibility of Gas1* to ERAD is caused by canonical remodeling of its GPI anchor, which occurs in all GPI-APs and provides a protein-independent ER export signal. Thus, GPI anchor remodeling is independent of protein folding and leads to efficient ER export of even misfolded species. Our data imply that ER quality control is limited for the entire class of GPI-APs, many of them being clinically relevant.
| S-EPMC4915193 | biostudies-literature
Project description:A system of endoplasmic reticulum (ER) chaperones has evolved to optimize the output of properly folded secretory and membrane proteins. An important player in this network is Glucose Regulated Protein 94 (GRP94). Over the last decade, new structural and functional data have begun to delineate the unique characteristics of GRP94 and have solidified its importance in ER quality control pathways. This review describes our current understanding of GRP94 and the four ways in which it contributes to the ER quality control: (1) chaperoning the folding of proteins; (2) interacting with other components of the ER protein folding machinery; (3) storing calcium; and (4) assisting in the targeting of malfolded proteins to ER-associated degradation (ERAD).
| S-EPMC3676867 | biostudies-literature
Project description:Recent work has highlighted the fact that lysosomes are a critical signaling hub of metabolic processes, providing fundamental building blocks crucial for anabolic functions. How lysosomal functions affect other cellular compartments is not fully understood. Here, we find that lysosomal recycling of the amino acids lysine and arginine is essential for proper ER quality control through the UPRER. Specifically, loss of the lysine and arginine amino acid transporter LAAT-1 results in increased sensitivity to proteotoxic stress in the ER and decreased animal physiology. We find that these LAAT-1–dependent effects are linked to glycine metabolism and transport and that the loss of function of the glycine transporter SKAT-1 also increases sensitivity to ER stress. Direct lysine and arginine supplementation, or glycine supplementation alone, can ameliorate increased ER stress sensitivity found in laat-1 mutants. These data implicate a crucial role in recycling lysine, arginine, and glycine in communication between the lysosome and ER.
| S-EPMC7319768 | biostudies-literature
Project description:We induced ER stress in Jurkat T-cells with dithiothreitol (DTT), which reduces the protein disulfide bonds and causes the accumulation of misfolded proteins in the ER lumen. For assessment of DTT effects on cells, we performed Affymetrix whole transcriptome gene expression analysis. The cells were treated for 6 hours with 2.5 mM Dithiothreitol (Sigma-Aldrich). Total RNA was isolated from DTT-treated (2 replicates) and control (2 replicates) Jurkat cells and hybridized to a gene expression arrays (GeneChip Gene 1.0 ST Array System; Affymetrix, Santa Clara, CA).
2017-04-15 | E-MTAB-5574 | biostudies-arrayexpress