Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA599329 | ENA |
REPOSITORIES: ENA
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Project description:Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR)
| PRJNA137213 | ENA
Project description:AtbZIP60 is one of the transcription factors involved in the endoplasmic reticulum (ER) stress response in Arabidopsis. To identify genes under the control of AtbZIP60 during ER stress, we compared the genome-wide expression profiles of wild-type and atbzip60 mutant plants in response to the ER stress inducer tunicamycin.
2008-11-19 | E-MEXP-1753 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by excessive desmoplasia and autophagy-dependent tumorigenic growth. Pancreatic stellate cells (PSCs) as a predominant stromal cell type play a critical role in PDAC biology. Autophagy facilitates PSC activation. However, the mechanism remains unknown. To investigate the mechanism of autophagy in PSC activation, gene expression profiles between patient-derived PSCs from pancreatic cancer and chronic pancreatitis were compared using a gene expression microarray. Here, we found that endoplasmic reticulum aminopeptidase 2 (ERAP2), which resides in the endoplasmic reticulum (ER) membrane, was highly expressed in both cancer-associated PSCs and pancreatic cancer cells (PCCs). We found that high stromal ERAP2 expression is associated with a poor prognosis of PDAC patients. Knockdown of ERAP2 inhibited autophagy of PSCs and PCCs. In PSCs, inhibition of autophagy by ERAP2 knockdown led to inactivation of PSCs and attenuated tumor-stromal interactions. This process was mediated by ER stress and consequent IRE1α and PERK unfolded protein response (UPR) signaling pathways. In orthotopic models, ERAP2 knockdown in PSCs inhibited growth and fibrosis of xenografted tumor compared with coimplantation of PSCs without ERAP2 knockdown, and gemcitabine treatment further inhibited tumor growth. Our findings demonstrate a novel mechanism of PSCs activation regulated by autophagy. ERAP2 as a promising therapeutic target may provide a novel strategy for the treatment of PDAC.
2022-04-30 | GSE172168 | GEO
Project description:To investigate whether ER stress underpins the secretion of mis-glycosylated glycoproteins by trophoblast, we treated trophoblast-like BeWo cells with the ER stress inducer thapsigargin (Tg), an inhibitor specific for sarco/endoplasmic reticulum Ca2+-ATPase.
2022-12-04 | E-MTAB-10943 | biostudies-arrayexpress
Project description:Ribosome footprinting in the cytosol and endoplasmic reticulum
| PRJNA145711 | ENA
Project description:The Unfolded Protein Response (UPR) is an adaptive pathway that restores cellular homeostasis after endoplasmic reticulum (ER) stress caused by an impairment of its protein folding capacity. The ER-resident kinase/ribonuclease Ire1 is the only UPR sensor that has been conserved during evolution from yeast to mammals; in these organisms, Ire1 transmits information from the ER to the nucleus trough the non-conventional splicing of Hac1 (yeast)/Xbp1 (metazoans) mRNA. We described the Dictyostelium discoideum ER-stress response and characterized its single bonafide Ire1 orthologue, IreA. We found that tunicamycin (TN) triggers a gene-expression program that increases the protein folding capacity of the ER and that alleviates ER protein load. Further, IreA resulted essential not only for cell-survival after TN-induced ER-stress, but also to accomplish about nearly 40% of the transcriptional changes induced upon a TN treatment. In addition, we described that autophagy is activated in Dictyostelium cells after a TN treatment and that autophagy-defective mutants exhibited increased sensitivity to this drug. The response of Dictyostelium cells to ER-stress involves the combined activation of an IreA-dependent gene expression program and the autophagy pathway.
2018-04-28 | GSE104409 | GEO
Project description:Lysosomal-autophagic degradation of Endoplasmic Reticulum via autophagy (ER-phagy) is emerging as critical regulator of ER homeostasis and function. However, the molecular mechanisms governing ER-phagy are still unknown. Working in chondrocytes, we found that ER-phagy and lysosome biogenesis are co-activated by FGF signaling during hypertrophic differentiation, a mandatory step for bone formation. FGF induced ER-phagy trough IRS1-dependent inhibition of the insulin signaling and activation of MiT/TFE transcription factors, master regulators of lysosome biogenesis. MiT/TFE promoted ER-phagy through the induction of the ER-phagy receptor FAM134B. Notably, the activation of ER-phagy promotes chondrocytes differentiation and secretion of factors required for cartilage replacement by bone. Consistently, medaka fish knock-down for FAM134B have impaired ossification of cranial bones. Thus, ER-phagy is a transcriptionally regulated process that participates to cell differentiation during development.
2020-07-15 | PXD015331 | Pride
Project description:Pancreatic beta-cell dysfunction and death are central in the pathogenesis of type 2 diabetes. Saturated fatty acids cause beta-cell failure and contribute to diabetes development in genetically predisposed individuals. Here we used RNA-sequencing to map transcripts expressed in five palmitate-treated human islet preparations, observing 1,325 modified genes. Palmitate induced fatty acid metabolism and endoplasmic reticulum (ER) stress. Functional studies identified novel mediators of adaptive ER stress signaling. Palmitate modified genes regulating ubiquitin and proteasome function, autophagy and apoptosis. Inhibition of autophagic flux and lysosome function contributed to lipotoxicity. Palmitate inhibited transcription factors controlling beta-cell phenotype including PAX4 and GATA6. 59 type 2 diabetes candidate genes were expressed in human islets, and 11 were modified by palmitate. Palmitate modified expression of 17 splicing factors and shifted alternative splicing of 3,525 transcripts. Ingenuity Pathway Analysis of modified transcripts and genes confirmed that top changed functions related to cell death. DAVID analysis of transcription binding sites in palmitate-modified transcripts revealed a role for PAX4, GATA and the ER stress response regulators XBP1 and ATF6. This human islet transcriptome study identified novel mechanisms of palmitate-induced beta-cell dysfunction and death. The data point to crosstalk between metabolic stress and candidate genes at the beta-cell level. 5 human islet of Langerhans preparations examined under 2 conditions (control and palmitate treatment)
2014-01-09 | E-GEOD-53949 | biostudies-arrayexpress
Project description:DNA damage and metabolic disorders are intimately linked with premature disease onset but the underlying mechanisms remain poorly understood. Persistent DNA damage accumulation in tissue-infiltrating macrophages carrying an ERCC1-XPF DNA repair defect (Er1F/-) riggers Golgi dispersal, dilation of endoplasmic reticulum, autophagy and exosome biogenesis leading to the secretion of extracellular vesicles (EVs) in vivo and ex vivo.
2019-11-04 | E-MTAB-8439 | biostudies-arrayexpress