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Title: The inducuction of UPR target genes in response to zinc depletion and serum starvation in HeLa cells      
dateReleased:
08-09-2013
description:
Zinc is an essential trace element, and impaired zinc homeostasis is implicated in the pathogenesis of various human diseases. However, the mechanisms cells use to respond to zinc deficiency are poorly understood. We previously reported that amyotrophic lateral sclerosis (ALS)-linked pathogenic mutants of SOD1 cause chronic ER stress through specific interactions with Derlin-1, which is a component of the ER-associated degradation machinery. Moreover, we recently demonstrated that this interaction is common to ALS-linked SOD1 mutants, and SOD1WT comprises a masked Derlin-1-binding region. We found that under serum starved and zinc-deficient conditions, SOD1WT adopts a mutant-like conformation that exposes the Derlin-1-binding region, suggesting that SOD1-Derlin-1 interaction may contribute to induce ER stress under these conditions. Using RNA microarrays, we revealed that the zinc depletion and serum starvation induce the expression of the unfolded protein response (UPR) target genes, including HSPA5/BiP, SEL1L, DNAJC3/p58, and ARMET. We conclude that SOD1 has a novel function as a molecular switch that activates the ER stress response under zinc-deficient conditions HeLa cells were treated with 8µM TPEN for 9h or exposured to 36h of serum starvation with or without 30µM zinc.Then the total RNA was isolated from cells using the Isogen reagent (Wako) following the manufacturer's recommendations.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-49657
refinement:
raw
alternateIdentifiers:
49657
keywords:
functional genomics
dateModified:
06-03-2014
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-AGIL-28
name:
Agilent Whole Human Genome Microarray 4x44K 014850 G4112F (85 cols x 532 rows)
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-49657/E-GEOD-49657.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-49657/E-GEOD-49657.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49657
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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