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GSE20667
Homo sapiens
20 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The NF-B pathway is a critical regulator of the immune system and has been implicated in cellular transformation and tumorigenesis. NF-B response is regulated by the activation state of the IB kinase (IKK) complex and triggered by a wide spectrum of stimuli. We previously reported that NF-B is downstream of Notch1 in T cell acute lymphoblastic leukaemia (T-ALL), however both the mechanisms involving Notch1-induced NF-B activation and the potential importance of NF-B in the maintenance of the disease are unknown. Here we visualize Notch-induced NF-B activation using both human T-ALL cell lines and animal models of this type of leukemia. We show that it is not Notch1 itself but Hes1, a canonical Notch target, the responsible for sustaining IKK activation in T-ALL. Hes1 exerts its effects by a direct transcriptional repression of the deubiquitinating enzyme CYLD, a well-characterized IKK inhibitor. Consistently, CYLD expression is significantly reduced in primary T-ALL leukemias. Finally, we demonstrate that IKK complex inhibition is a promising option for the targeted therapy of T-ALL as suppression of IKK function affected both the survival of human T-ALL cells in vitro and the maintenance of the disease in vivo.
Publication Title
The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To define the characteristics of human oral mucosa fibroblasts (hOFs), we analyzed the gene expression of hOFs compared with that of human dermal fibroblasts (hDFs), and that of hOF-derived induced pluripotent stem cells (hOF-iPSCs).
Publication Title
Gene Signature of Human Oral Mucosa Fibroblasts: Comparison with Dermal Fibroblasts and Induced Pluripotent Stem Cells.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Pseudomonas aeruginosa pao1, Pseudomonas aeruginosa
- 8 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The putative trancriptional regulator PA2449 was found to be essential for both glycine/serine metabolism and the production of phenazines in P. aeruignosa PAO1.
Publication Title
Gene PA2449 is essential for glycine metabolism and pyocyanin biosynthesis in Pseudomonas aeruginosa PAO1.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
We did transcription profiling on the effect of rlm1 (MAPK Slt2 transcription factor) deletion and swi3 (component of SWI/SNF complex involved in chromatin remodeling) deletion in genes involved in cell wall stress (Congo Red) response.
Publication Title
Chromatin remodeling by the SWI/SNF complex is essential for transcription mediated by the yeast cell wall integrity MAPK pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa pao1
- 6 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The transcriptome of P. aeruginosa PAO1 in the presence of extracelluar 2-oxoglutarate at a concentration of 20 mM.
Publication Title
Genetic analysis of the assimilation of C5-dicarboxylic acids in Pseudomonas aeruginosa PAO1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To understand the molecular mechanism underlying inflammatory reaction in vascular system post exposure to ionizing radiation, we carried out microarray analysis in HUVEC exposed with X-ray
Publication Title
Comprehensive and computational analysis of genes in human umbilical vein endothelial cells responsive to X-irradiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Skeletal muscle mass is an important determinant of whole-body glucose disposal. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3'-phosphoinositide–dependent kinase 1 (PDK1), a key component of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of exercise load–induced muscle hypertrophy.
Publication Title
Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load.
Sample Metadata Fields
Sex, Specimen part
View Samples- Schizosaccharomyces pombe
- 3 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Wild-type cells were cultured at 30 deg and cells were harvested. Total RNAs were purified from 3 populations.
Publication Title
Mapping of long-range associations throughout the fission yeast genome reveals global genome organization linked to transcriptional regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Infliximab (IFX) has been reported as the further therapy in intravenous immunoglobulin G (IVIG)-resistant Kawasaki disease (KD) patients. IFX is a monoclonal antibody that blocks the pro-inflammatory cytokine tumor necrosis factor (TNF)-, but how IFX affect KD vasculitis is unknown. We investigated expression profiling of whole blood cells to elucidate the molecular mechanisms of the effectiveness of IFX therapy and to find characteristic biomarker and an important target in refractory KD. Methods: Refractory KD patients who failed to respond to repeated intravenous immunoglobulin G (IVIG) infusions had received a single infusion of IFX as third therapy. To validate specifically transcripts abundance for IFX therapy, we detected the altered transcripts expression and signaling pathways of whole blood mRNA in these IFX-responsive patients (n=8) using Affymetrix array, comparing initial IVIG-responsive patients (n=6).Results: A total of 1,388 transcripts abundance were significantly altered before and after IFX treatment. These transcripts abundance in IFX had Nucleotide-binding oligomerization domain pathway that play a role in activation of NFB and IL-1 signaling pathway outside the field of TNF- signaling pathway. Fifty transcripts including Peptidase inhibitor-3 (PI3), Matrix metalloproteinase-8 (MMP8), Chemokine (C-C motif) receptor-2 (CCR2) and Pentraxin-3 (PTX3) were significantly down-regulated in IFX. Conclusion: We demonstrated that the inhibition of TNF- by IFX have affected various molecular mechanism materially for IVIG-resistant KD patients.
Publication Title
Transcriptional regulation by infliximab therapy in Kawasaki disease patients with immunoglobulin resistance.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
Illumina HiSeq 2000
Description
Unlike other members of the MAPK family, ERK5 contains a large C-terminal domain with transcriptional activation capability in addition to an N-terminal canonical kinase domain. Genetic deletion of ERK5 is embryonic lethal and tissue-restricted deletions have profound effects on erythroid development, cardiac function and neurogenesis. In addition, depletion of ERK5 is anti-inflammatory and anti-tumorigenic. Small molecule inhibition of ERK5 has been shown to have promising activity in cell and animal models of inflammation and oncology. Here we report the synthesis and biological characterization of potent, selective ERK5 inhibitors. In contrast to both genetic depletion/deletion of ERK5 and inhibition with previously reported compounds, inhibition of the kinase with the most selective of the new inhibitors had no anti-inflammatory or anti-proliferative activity. The source of efficacy in previously reported ERK5 inhibitors is shown to be off-target activity on bromodomains (BRDs), conserved protein modules involved in recognition of acetyl-lysine residues during transcriptional processes. It is likely that phenotypes reported from genetic deletion or depletion of ERK5 arise from removal of a non-catalytic function of ERK5. The newly reported inhibitors should be useful in determining which of the many reported phenotypes are due to kinase activity, and delineate which can be pharmacologically targeted. Overall design: Two cellular models with reported ERK5-regulated signaling were used: Pam3CSK4-stimulated HUVECs as a model of inflammation, and EGF-stimulated HeLa cells as an established cell model of ERK5 regulation. Cells were pre-incubated with DMSO vehicle, AX15836 (ERK5 inhibitor), AX15839 (dual ERK5/BRD inhibitor), or I-BET762 (BRD inhibitor), then stimulated with agonist. Cellular responses were verified by immunoassays and western blots using replicate wells in the same experiment.
Publication Title
ERK5 kinase activity is dispensable for cellular immune response and proliferation.
Sample Metadata Fields
Specimen part, Subject, Compound
View Samples