Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Parkinson's disease-associated DJ-1 is required for the expression of GDNF receptor Ret in human neuroblastoma cells

ABSTRACT: DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. To explore DJ-1-mediated transcriptional control in Parkinson’s disease (PD), we generated human neuroblastoma cells with inducible knock-down of DJ-1 expression. We then used functional genomic techniques to identify novel pathways dysregulated by loss of DJ-1 function. Using microarray gene expression profiling, we found that DJ-1 silencing alters the expression of 26 genes, with 10 down-regulated and 16 up-regulated transcripts. Among the down-regulated genes we found Ret, tyrosine kinase receptor for the neurotrophic factor GDNF. Taking advantage of Ingenuity Pathways Analysis, we identified hypoxia inducible factor 1 alpha (Hif1a) as a possible mediator of the interplay between DJ-1 and Ret. We show that Hif1a is stabilized in the absence of DJ-1, and that loss of DJ-1 generates hypoxia and accumulation of free radical species (ROS). Overexpression of wt DJ-1, but not of C106A and L166P mutants deficient in ROS scavenger activity, rescues Ret expression in neuroblastoma cells. These findings reveal novel players in PD pathogenesis and provide evidence for additional pathways involved in DJ-1-mediated neurodegeneration.

ORGANISM(S): Homo sapiens

PROVIDER: GSE17204 | GEO | 2010/04/16

SECONDARY ACCESSION(S): PRJNA119215

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Parkinson's disease-associated DJ-1 is required for the expression of GDNF receptor Ret in human neuroblastoma cells

Project description:DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. To explore DJ-1-mediated transcriptional control in Parkinsonâ??s disease (PD), we generated human neuroblastoma cells with inducible knock-down of DJ-1 expression. We then used functional genomic techniques to identify novel pathways dysregulated by loss of DJ-1 function. Using microarray gene expression profiling, we found that DJ-1 silencing alters the expression of 26 genes, with 10 down-regulated and 16 up-regulated transcripts. Among the down-regulated genes we found Ret, tyrosine kinase receptor for the neurotrophic factor GDNF. Taking advantage of Ingenuity Pathways Analysis, we identified hypoxia inducible factor 1 alpha (Hif1a) as a possible mediator of the interplay between DJ-1 and Ret. We show that Hif1a is stabilized in the absence of DJ-1, and that loss of DJ-1 generates hypoxia and accumulation of free radical species (ROS). Overexpression of wt DJ-1, but not of C106A and L166P mutants deficient in ROS scavenger activity, rescues Ret expression in neuroblastoma cells. These findings reveal novel players in PD pathogenesis and provide evidence for additional pathways involved in DJ-1-mediated neurodegeneration. Comparison between DJ-1-silenced human SH-SY5Y neuroblastoma cells and control cells. Two clones were selected for each condition, and each clone was analyzed in duplicate, for a total of 8 samples.

2010-04-28 | E-GEOD-17204 | biostudies-arrayexpress

Gene expression analysis of androgen treatment and stable HIF1a expression in LNCaP cell line

Project description:Androgen receptor (AR) and hypoxia inducible factor 1a (HIF1a) are transcription factors that promote prostate cancer progression. This study investigated the relationship between the AR and HIF1a signaling pathways. Gene expression analysis identified transcriptional changes in response to androgen treatment and stable HIF1a expression.

2019-05-15 | GSE114500 | GEO

ChIP-seq analysis of HIF and AR binding sites in LNCaP cell line

Project description:Androgen receptor (AR) and hypoxia inducible factor 1a (HIF1a) are transcription factors that promote prostate cancer progression. This study investigated the relationship between the AR and HIF1a signaling pathways. ChIP-seq analysis was performed on the LNCaP cell line to identify global HIF and AR binding sites within the genome, under hypoxia and normoxia and in the presence and absence of androgen treatment.

2019-05-15 | GSE114732 | GEO

Identification of interacting proteins of lncRNA HIF1α-AS1

Project description:LncRNA Hypoxia-inducible factor 1α-antisense 1 (HIF1α-AS1) is located on the antisense strand of the important Hypoxia-inducible factor 1α (HIF1α) gene, but being transcribed in antisense direction along the HIF1α promoter. Here we used the 3’end biotinylated HIF1a-AS1 RNA and a control RNA for RNA Pulldown and searched for interacting proteins in nuclear extracts of human umbilical vein endothelial cells (HUVEC).

2022-09-23 | PXD023512 | Pride

Hypoxia-independent downregulation of hypoxia inducible factor 1 targets by androgen deprivation therapy in prostate cancer.

Project description:Hypoxia inducible factor 1 (HIF1) has been shown to cooperate with the androgen receptor (AR) in activation of oncogenic pathways in prostate cancer (PCa). Here we hypothesized that HIF1 also plays a role in PCa response to androgen deprivation therapy (ADT). Comparison of gene expression profiles of androgen exposed (AE) and androgen deprived (AD) CWR22 PCa xenografts identified 596 upregulated and 748 downregulated genes after ADT. Gene ontology (GO) analysis of the differentially expressed genes showed significant enrichment of the biological processes cell proliferation, cell cycle and metabolism and suggested suppression of these processes after ADT. A set of 80 hypoxia-inducible genes were identified in 22Rv1 and LNCaP cell lines treated with hypoxia and showed considerable overlap (53%) with the downregulated genes. Immunostaining of the hypoxia marker pimonidazole showed no difference between AE- and AD-tumors. Comparison of the differentially expressed genes with lists of 1115 direct AR- and 276 direct HIF1-target genes identified 138 AR- and 40 HIF1-targets that were regulated after ADT, including six shared AR- and HIF1-targets for which downregulation was confirmed with RT-PCR. Most HIF1-targets were downregulated and included in the significant biological processes and the set of hypoxia-inducible genes. The downregulation of HIF1-targets was consistent with decreased HIF1A immunostaining in AD- compared to AE-tumors (p=0.002). A decrease in HIF1A immunostaining after ADT was also demonstrated in a cohort of 35 PCa patients (p<0.001). These data suggest suppressed HIF1-signaling after ADT and a shared role of HIF1 and AR in the regressive phase of PCa after ADT. Prostate cancer xenografts were subjected to adrogen deprivation therapy and analysed with regard to changes in gene expressions. Cell culture experiments were performed to generate prostate cancer specific gene lists associated with hypoxia.

2013-10-02 | E-GEOD-42868 | biostudies-arrayexpress

Genome-wide analysis of gene expression in DJ-1 deficient muscle cells

Project description:Excessive reactive oxygen species (ROS) underlie the pathogenesis of multiple disorders. Nevertheless, physiological levels of ROS are required for intracellular signalling and maintenance of metabolic homeostasis. DJ-1, a Parkinson’s disease-associated protein, is involved in the regulation of oxidative stress. Our aim in this study was to determine the effect of DJ-1 disruption on gene expression in muscle cells. To this end, we transfected a murine myoblast cell line, C2C12 cells with siRNA targeting DJ-1.

2014-11-07 | GSE63051 | GEO

Genome-wide maps of HIF1a binding sites in ccRCC cell line under hypoxia condition

Project description:We report the application of chromatin immunoprecipitation and next generation sequencing technology for HIF1a binding sites at genome wide level in a RCC (renal cell carcinoma) cell line under hypoxia conditions. We found HIF1a binding sites in Caki-2 cell line under hypoxia conditions. Especially, we found HIF1a bind to SPOP under hypoxia condition, which was further validated. Examination of HIF1a binding sites in Caki-2 cell line under hypoxia condition

2014-03-27 | E-GEOD-54327 | biostudies-arrayexpress

Activation of g-globin expression by hypoxia-inducible factor 1a [CUT&RUN]

Project description:Longstanding observations that fetal hemoglobin (HbF, a2g2) expression is reactivated in postnatal red blood cells (RBCs) during hypoxia or recovery from anemia remain unexplained. We identified the hypoxia inducible factor (HIF) signaling pathway as a direct regulator of HbF expression in a CRISPR/Cas9 genetic screen. In RBC precursors, depletion of the von Hippel–Lindau (VHL) E3 ligase stabilized its ubiquitination target HIF1a to induce g-globin gene transcription. Mechanistically, HIF1a-HIF1bheterodimers bound cognate DNA elements in BGLT3, a long-noncoding RNA gene located 2.7 kb downstream of the tandem g-globin genes. This was followed by recruitment of transcriptional activators, chromatin opening, and increased long-range interactions between the g-globin genes and their upstream enhancer. These effects were recapitulated by hypoxia or inhibition of prolyl hydroxylase domain (PHD) enzymes that target HIF1a for ubiquitination. Our findings link globin gene regulation with canonical hypoxia adaptation, elucidate a mechanism for HbF induction during stress erythropoiesis, and identify a novel therapeutic approach for β-hemoglobinopathies.

2022-07-14 | GSE204900 | GEO

Activation of g-globin expression by hypoxia-inducible factor 1a [RNA-seq]

2022-07-14 | GSE184459 | GEO

Activation of g-globin expression by hypoxia-inducible factor 1a [CaptureC]

2022-07-14 | GSE204899 | GEO