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GSE38392
Homo sapiens
7 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Identification of druggable targets is a prerequisite for developing targeted therapies against Ewing sarcoma. We report the identification of Protein Kinase C Beta (PRKCB) as a protein specifically and highly expressed in Ewing sarcoma as compared to other pediatric cancers. Its transcriptional activation is directly regulated by the EWSR1-FLI1 oncogene. Getting insights in PRKCB activity we show that, together with PRKCA, it is responsible for the phosphorylation of histone H3T6, allowing global maintenance of H3K4 trimethylation on a variety of gene promoters. In the long term, PRKCB RNA interference induces apoptosis in vitro. More importantly, in xenograft mice models, complete impairment of tumor engraftment and even tumor regression were observed upon PRKCB inhibition, highlighting PRKCB as a most valuable therapeutic target. Deciphering PRKCB roles in Ewing sarcoma using expression profiling, we found a strong overlap with genes modulated by EWSR1-FLI1 and an involvement of RPKCB in regulating crucial signaling pathways. Altogether, we show that PRKCB may have two important independent functions and should be considered as highly valuable for understanding Ewing sarcoma biology and as a promising target for new therapeutic approaches in Ewing sarcoma.
Publication Title
Targeting the EWSR1-FLI1 oncogene-induced protein kinase PKC-β abolishes ewing sarcoma growth.
Sample Metadata Fields
Cell line
View Samples- Escherichia coli
- 2 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Antitoxins are becoming recognized as proteins that regulate more than their own synthesis; for example, we found previously that antitoxin MqsA represses the gene encoding the stationary phase sigma factor RpoS. Here, we investigated the physiological role of antitoxin DinJ of the DinJ/YafQ toxin/antitoxin system and found DinJ also affects the general stress response by decreasing RpoS levels. Corroborating the reduced RpoS levels upon producing DinJ, catalase activity, cell adhesins, and cyclic diguanylate decreased while swimming increased. Using a transcriptome search and DNA-binding assays, we determined that the mechanism by which DinJ reduces RpoS is by repressing cspE which encodes cold-shock protein CspE that inhibits translation of rpoS mRNA. Hence, DinJ influences the general stress response indirectly by regulating cspE.
Publication Title
Antitoxin DinJ influences the general stress response through transcript stabilizer CspE.
Sample Metadata Fields
Time
View Samples- Citrus sinensis
- 12 Downloadable Samples
- Affymetrix Citrus Genome Array (citrus)
Description
We have used the citrus GeneChip array (GPL5731) to survey the transcription profiles of sweet orange in response to the bacterial pathogens Xanthomonas axonopodis pv. citri (Xac) and Xanthomonas axonopodis pv. aurantifolii (Xaa). Xac is the causal agent of the citrus canker disease on a wide range of citrus species, including sweet oranges (Citrus sinensis). On the other hand, Xaa is pathogenic to Mexican lime (Citrus aurantifolia) only, and in sweet orange it triggers a defense response. In order to identify the genes induced during the defense response (Xaa-responsive genes) or citrus canker development (Xac-responsive genes), we conducted microarrays hybridization experiments at 6 and 48 hours after bacterial infiltration (habi). The analysis revealed that genes commonly modulated by Xac and Xaa are associated with basal defenses normally triggered by pathogen-associated molecular patterns, including those involved in reactive oxygen species production and lignification. Significantly, Xac-infected leaves showed considerable changes in the transcriptional profiles of defense-, cell wall-, vesicle trafficking- and cell growth-related genes between 6 and 48 habi. This is consistent with the notion that Xac suppresses host defenses near the beginning of the infection and simultaneously changes the physiological status of the host to promote cell enlargement and division. Finally, Xaa triggered a MAP kinase signaling pathway involving WRKY and ethylene-responsive transcriptional factors known to activate downstream defense genes.
Publication Title
Transcriptional analysis of the sweet orange interaction with the citrus canker pathogens Xanthomonas axonopodis pv. citri and Xanthomonas axonopodis pv. aurantifolii.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli k-12
- 2 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Persister cells are a sub-population of all bacterial cultures which exhibit a non-inheritable, multi-drug tolerance when subjected to lethal antibiotic challenge. These persisters arise as a result of metabolic dormancy, and can resume growth subsequent to antibiotic challenge, leading to recalcitrance of bacterial infections.
Publication Title
Phosphodiesterase DosP increases persistence by reducing cAMP which reduces the signal indole.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Arabidopsis thaliana
- 21 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Exposure to high irradiance results in dramatic changes in nuclear gene expression in plants. However, little is known about the mechanisms by which changes in irradiance are sensed and how the information is transduced to the nucleus to initiate the genetic response. To investigate whether the photoreceptors are involved in the response to high irradiance, we analyzed expression of ELIP1, ELIP2, APX2 and LHCB2.4 in the phyA, phyB, cry1 and cry2 photoreceptor mutants and hy5 and hyh transcription factor mutants. Following exposure to high intensity white light for 3 h (HL, 1000 micro mol quanta m-2 s-1) expression of ELIP1/2 and APX2 was strongly induced and LHCB2.4 expression repressed in wild type. The cry1 and hy5 mutants showed specific mis-regulation of ELIP1/2 and we show that the induction of ELIP1/2 expression is mediated via CRY1 in a blue light intensity-dependent manner. Furthermore, using the Affymetrix Arabidopsis 24K Gene-Chip we showed that 77 of the HL responsive genes are regulated via CRY1, and 26 of those genes were also HY5 dependent. As a consequence of the mis-regulation of these genes the cry1 mutant displayed a high irradiance-sensitive phenotype with significant photoinactivation of PSII, indicated by reduced Fv/Fm. Thus, we describe a novel function of CRY1 in mediating plant responses to high irradiances that is essential to the induction of photoprotective mechanisms. This indicates that high irradiance can be sensed in a chloroplast-independent manner by a cytosolic/nucleic component.
Publication Title
Genome-wide gene expression analysis reveals a critical role for CRYPTOCHROME1 in the response of Arabidopsis to high irradiance.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In addition to the glucocorticoids, the glucocorticoid receptor (GR) is regulated by post-translational modifications, including SUMOylation. We have analyzed how SUMOylation influences the activity of endogenous GR target genes and the receptor chromatin binding by using isogenic HEK293 cells expressing wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR). Gene expression profiling revealed that both dexamethasone up- and down-regulated genes are affected by the GR sumoylation and that the affected genes are significantly associated with pathways of cellular proliferation and survival. The GR3KR-expressing cells proliferated more rapidly and their anti-proliferative response to dexamethasone was less pronounced than in the wtGR-expressing cells. ChIP-seq analyses indicated that the SUMOylation modulates the chromatin occupancy of GR on several loci associated with cellular growth in a fashion which parallels with their differential dexamethasone-regulated expression between the two cell lines. Moreover, genome-wide SUMO-2/3 marks, which were generally associated with active chromatin, showed markedly higher overlap with the wtGR cistrome than with the GR3KR cistrome. In sum, our results indicate that the SUMOylation does not simply repress the GR activity, but regulates the activity of the receptor in a target locus selective fashion, playing an important role in controlling the GR activity on genes influencing cell growth.
Publication Title
SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In addition to the glucocorticoids, the glucocorticoid receptor (GR) is regulated by post-translational modifications, including SUMOylation. We have analyzed how SUMOylation influences the activity of endogenous GR target genes and the receptor chromatin binding by using isogenic HEK293 cells expressing wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR). Gene expression profiling revealed that both dexamethasone up- and down-regulated genes are affected by the GR sumoylation and that the affected genes are significantly associated with pathways of cellular proliferation and survival. The GR3KR-expressing cells proliferated more rapidly and their anti-proliferative response to dexamethasone was less pronounced than in the wtGR-expressing cells. ChIP-seq analyses indicated that the SUMOylation modulates the chromatin occupancy of GR on several loci associated with cellular growth in a fashion which parallels with their differential dexamethasone-regulated expression between the two cell lines. Moreover, genome-wide SUMO-2/3 marks, which were generally associated with active chromatin, showed markedly higher overlap with the wtGR cistrome than with the GR3KR cistrome. In sum, our results indicate that the SUMOylation does not simply repress the GR activity, but regulates the activity of the receptor in a target locus selective fashion, playing an important role in controlling the GR activity on genes influencing cell growth.
Publication Title
SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
RAS oncogenic mutations are common in human cancers, but RAS proteins have been difficult to target. We sought to identify pharmacological agents to block the RAS oncogenic signaling by a distinct mechanism. Since the biological activity of RAS proteins rely upon lipid modifications and RAS regulates lipid metabolisms in cancer cells, we screened a bioactive lipid library using a RAS specific cell viability assay. We report the discovery of a new class of inhibitors for RAS transformation. Compounds in the class represented by endocannabinoid N-arachidonoyl dopamine (NADA) can induce cell oncosis, independent of its ability to engage cannabinoid receptors. Further analyses show that NADA is more active in inhibiting the NRAS transformation and signaling than that of KRAS4B. Mechanistically, NADA blocks the plasma membrane translocation of NRAS, but not that of KRAS4B. In addition, NADA inhibits the plasma membrane translocation and neoplastic transformation of oncogenic KRAS4A. Interestingly, NADA also redistributes the cytoplasmic NRAS to the Golgi apparatus in a palmitoylation-dependent manner. The results indicate that NADA inhibits NRAS and KRAS4A plasma membrane translocation by targeting a novel molecular process. The new findings would help to develop novel targeted therapies for a broad range of human cancers.
Publication Title
N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The mammalian innate immune system senses many bacterial stimuli through the toll-like receptor (TLR) family. Activation of the TLR4 receptor by bacterial lipopolysaccharide (LPS) is the most widely studied TLR pathway due to its central role in host responses to gram-negative bacterial infection and its contribution to endotoxemia and sepsis. Here we describe a genome-wide siRNA screen to identify genes regulating the mouse macrophage TNF- and NF-B responses to LPS. We include a secondary validation screen conducted with six independent siRNAs per gene to facilitate removal of off-target screen hits. We also provide microarray data from the same LPS-treated macrophage cells to facilitate downstream data analysis. These data provide a resource for analyzing gene function in the predominant pathway driving inflammatory signaling and cytokine expression in mouse macrophages.
Publication Title
Genome-wide siRNA screen of genes regulating the LPS-induced NF-κB and TNF-α responses in mouse macrophages.
Sample Metadata Fields
Specimen part, Cell line
View Samples