Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HepG2-MEK Inhibition with PD98059

ABSTRACT: Transcripts (mRNA) during amino acid limitation after MEK was inhibited were analyzed. HepG2 cells were pretreated with MEK inhibitor, PD98059 for 1 hour, then incubated in complete medium and a medium depleted for Histidine for 8 hours. For Inhibitor treated cells, PD98059 was included in the medium during the following 8 hours-incubation.

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Kilberg

PROVIDER: E-GEOD-58869 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

A mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-dependent transcriptional program controls activation of the early growth response 1 (EGR1) gene during amino acid limitation.

Shan Jixiu J Balasubramanian Mukundh N MN Donelan William W Fu Lingchen L Hayner Jaclyn J Lopez Maria-Cecilia MC Baker Henry V HV Kilberg Michael S MS

The Journal of biological chemistry 20140715 35

Amino acid (AA) limitation in mammalian cells triggers a collection of signaling cascades jointly referred to as the AA response (AAR). In human HepG2 hepatocellular carcinoma, the early growth response 1 (EGR1) gene was induced by either AA deprivation or endoplasmic reticulum stress. AAR-dependent EGR1 activation was discovered to be independent of the well characterized GCN2-ATF4 pathway and instead dependent on MEK-ERK signaling, one of the MAPK pathways. ChIP showed that constitutively boun ...[more]

PMID: 25028509

Similar Datasets

Expression data from primary human leukocytes (peropheral blood mononuclear cells, PBMC) cultured in vitro with HIV-1MN, HIV-2NIH-Z, CpG-A ODN or media alone

Project description:HIV-1 and HIV-2 can both infect humans, but HIV-2 causes a slow progressing disease and is well controlled by the immune system for prolonged period of times. Here we tested acute response aainst HIV-1 and HIV-2 exposure in peripheral blood mononuclear cells (PBMC) from three indepednent donors. A total of 24 samples were analyzed. PBMC from three donors were cultured with Media alone, HIV-1MN, HIV-2NIH-Z or the TLR9 agonist CpG-A (4 conditions), and cells were harvested at 6h and 12h (2time points) for RNA extraction.

2014-07-02 | E-GEOD-58994 | biostudies-arrayexpress

The activation of IL-1-induced enhancers depends on TAK1 kinase activity and NF-kappaB p65 II

Project description:The inflammatory gene response requires activation of the protein kinase TAK1, but it is currently unknown how TAK1-derived signals coordinate transcriptional programs in the genome. We determined the genome-wide binding of the TAK1-controlled NF-M-NM-:B subunit p65 in relation to active enhancers and promoters of transcribed genes by ChIP-seq experiments. Out of 35,000 active enhancer regions, 410 H3K4me1-positive enhancers show interleukin (IL)-1-induced H3K27ac and p65 binding. Inhibition of TAK1, IKK2 or depletion of p65 blocked inducible enhancer activation and gene expression. As exemplified by the CXC chemokine cluster located on chromosome 4, the TAK1-p65 pathway also regulates the recruitment kinetics of the histone acetyltransferase CBP, of NF-M-NM-:B p50 and of AP-1 transcription factors to both, promoters and enhancers. This study provides a high resolution view of epigenetic changes occurring during the IL-1 response and allows the first genome-wide identification of a novel class of inducible p65 NF-M-NM-:B-dependent enhancers in epithelial cells. Two sets of experiments were performed as biological replicate series (rep1 and rep2) each comprising 5 dual-color microarray hybridizations. The two series were performed with inverted Cy-Dye allocation (Dye-swap). Human epithelial KB cells were treated with Interleukin-1-alpha (10ng/M-BM-5l) for 0.5h, 1h, 3h or 24h, or, were left untreated. An individual set of samples was treated identically with IL1a but after an initial preincubation for 1h with PD98059 (50 micromol/l). Each dual-color microarray represents a direct comparison of samples preincubated or not with PD98059.

2014-12-17 | E-GEOD-64237 | biostudies-arrayexpress

Comprehensive transcriptome profiling reveals multigene signatures in triple negative breast cancer

Project description:To develop and validate novel multigene signatures to facilitate individualized treatment of TNBC patients By integrating expression profiles of messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). We analysed 165 TNBC samples and 33 paired normal breast tissues using transcriptome microarrays. Tumor-specific mRNAs and lncRNAs were identified and correlated with patientsâ?? recurrence-free survival (RFS). Using Cox regression model, we built two multigene signatures incorporating mRNAs and lncRNAs. The prognostic and predictive accuracy of the signatures were tested in a training set of 165 TNBC patients and validated in another 101 TNBC patients.

2016-01-04 | E-GEOD-76250 | biostudies-arrayexpress

Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target [Affymetrix]

Project description:in this study we define an epigenomic profile of PRC2 (H3K27me3 and bivalent) tragets in four newly diagnosed MM patients. Using Oncomine database we demonstarte that PRC2 targets are underexpressed with advanced ISS stages and correlated to poor outcome. Pharmacological inhibition of UNC1999 showed anti-myeloma potential in vitro by activating the expression genes related to apoptosis and cell differenatiation. In this array the differences between the gene expression profiles of samll molecule inhibitor (UNC1999) of EZH2 and the control (UNC2400) have been tested. So multiple myeloma cell line INA-6 was treated with 2Î¼M of UNC1999 and UNC2400. This design contains three biological replicates.

2015-12-31 | E-GEOD-69251 | biostudies-arrayexpress

Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-12-31 | E-GEOD-69253 | biostudies-arrayexpress

Transcriptional Profiling Defines the Roles of ERK and p38 Kinases in Epidermal Keratinocytes

Project description:Epidermal keratinocytes respond to extracellular influences by activating cytoplasmic signal transduction pathways that change the transcriptional profiles of affected cells. To define responses to two such pathways, p38 and ERK, we used SB203580 and PD98059 as specific inhibitors, and identified the regulated genes after 1, 4, 24 and 48 hrs, using Affymetrix’ Hu133Av2 microarrays. Additionally, we compared genes specifically regulated by p38 and ERKs with those regulated by JNK and by all three pathways simultaneously. We find that the p38 pathway induces the expression of extracellular matrix and proliferation-associated genes, while suppressing microtubule-associated genes; the ERK pathway induces the expression of nuclear envelope and mRNA splicing proteins, while suppressing steroid synthesis and mitochondrial energy production enzymes. Both pathways promote epidermal differentiation and induce feedback inactivation of MAPK signaling. c-FOS, SRY and N-Myc appear to be the principal targets of the p38 pathway, Elk-1 SAP1 and HLH2 of ERK, while FREAC-4, ARNT and USF are common to both. The results for the first time comprehensively define the genes regulated by the p38 and ERK pathways in epidermal keratinocytes and suggest a list of targets potentially useful in therapeutic interventions. Human epidermal keratinocytes are grown in Keratinocyte Serum-Free Medium (Gibco) supplemented with 0.05 mg/ml bovine pituitary extract, 2.5 ng/ml epidermal growth factor, 0.09 mM CalCl2 and 1% penicillin/streptomycin (KGM). They are switched to Keratinocyte Serum Free-Media (Gibco) supplemented only with 1% penicillin/streptomycin (KBM) 24 h prior to commencing experiments. A set is left as controls, others treated with 5 uM JNK inhibitor SP600125, 15 uM p38 inhibitor SB203580, or 50 um ERK inhibitor PD98059. Timecourse of treated and parellel control samples over a 48 hr period was performed.

2013-09-05 | E-GEOD-50591 | biostudies-arrayexpress

Homo sapiens

Project description:HepG2-MEK Inhibition with PD98059

| PRJNA253819 | ENA

Expression data from H9 human embryonic stem cells (hESCs) differentiated to Early Mesoendoderm

Project description:We used microarrays to detail the global programme of gene expression during early hESC differentiation to Mesendoderm using FBS. Samples of hESCs were taken at undifferentiated state (0h), 8h of differentiation, 24h of differentiation, and 72h of differentiation with three replicates (A, B, and C) at each time point.

2016-03-22 | E-GEOD-74004 | biostudies-arrayexpress

Antidyskinetic effects of MEK inhibitor are associated with multiple neurochemical alterations in the striatum of hemiparkinsonian rats

Project description:L-DOPA-induced dyskinesia (LID) represents one of the major problems of the long-term therapy of patients with Parkinson's disease (PD). Although the pathophysiologic mechanisms underlying LID are not completely understood, activation of the extracellular signal regulated kinase (ERK) is recognized to play a key role. ERK is phosphorylated by mitogen-activated protein kinase kinase (MEK), and thus MEK inhibitor can prevent ERK activation. Here the effect of the MEK inhibitor PD98059 on LID and the associated molecular changes were examined. Rats with unilateral 6-OHDA lesions of the nigrostriatal pathway received daily L-DOPA treatment for three weeks, and abnormal involuntary movements (AIMs) were assessed every other day. PD98059 was injected in the lateral ventricle daily for 12 days starting from day 10 of L-DOPA treatment. Striatal molecular markers of LID were analyzed together with gene regulation using microarray. The administration of PD98059 significantly reduced AIMs. In addition, ERK activation and other associated molecular changes including ΔFosB were reversed in rats treated with the MEK inhibitor. PD98059 induced significant up-regulation of 418 transcripts and down-regulation of 378 transcripts in the striatum. Tyrosine hydroxylase (Th) and aryl hydrocarbon receptor nuclear translocator (Arnt) genes were down-regulated in lesioned animals and up-regulated in L-DOPA-treated animals. Analysis of protein levels showed that PD98059 reduced the striatal TH. These results support the association of p-ERK1/2, ΔFosB, p-H3 to the regulation of TH and ARNT in the mechanisms of LID, and pinpoint other gene regulatory changes, thus providing clues for identifying new targets for LID therapy.

2017-01-18 | GSE93695 | GEO

Copy number variation in Y chromosome multicopy genes is linked to a paternal parent-of-origin effect on CNS autoimmune disease in female offspring

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-01-16 | E-GEOD-65048 | biostudies-arrayexpress