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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression data of A375 melanoma cells after DMSO or MLN4924 treatment from 1 hour to 24 hour

ABSTRACT: Microarrays were used to determine the change in gene expression of genes involved in the CDT1/NAE pathway A375 cells were grown and then incubated in the presence of either DMSO as control or 650nM MLN4924. Cells were treated for 1, 2, 4, 8, and 24 hours. RNA extraction and hybridization on Affymetrix HG-U133Plus 2.0 arrays were performed.

ORGANISM(S): Homo sapiens

SUBMITTER: Hugues Bernard

PROVIDER: E-GEOD-30531 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Quantitative proteomic analysis of cellular protein modulation upon inhibition of the NEDD8-activating enzyme by MLN4924.

Liao Hua H Liu Xiaozhen J XJ Blank Jonathan L JL Bouck David C DC Bernard Hugues H Garcia Khristofer K Lightcap Eric S ES

Molecular & cellular proteomics : MCP 20110826 11

Cullin-RING ubiquitin ligases (CRLs) are responsible for the ubiquitination of many cellular proteins, thereby targeting them for proteasomal degradation. In most cases the substrates of the CRLs have not been identified, although many of those that are known have cancer relevance. MLN4924, an investigational small molecule that is a potent and selective inhibitor of the Nedd8-activating enzyme (NAE), is currently being explored in Phase I clinical trials. Inhibition of Nedd8-activating enzyme b ...[more]

PMID: 21873567

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Expression data of A375 melanoma cells after DMSO or MLN4924 +/- Nutlin treatment for 26 hours

Project description:Microarrays were used to determine the change in gene expression of genes involved in the p53 pathway after siRNA knock down of p53, CDT1 or BRCA1 A375 cells were grown, transfected with siRNA, incubated for 48hrs, then incubated for another 26hrs in the presence of either 0.065% DMSO as control, 650nM MLN4924, 5uM Nutlin or 100nM Daunorubicin. RNA extraction and hybridization on Affymetrix HG-U133Plus 2.0 arrays were performed. 12 conditions in triplicate for a total of 42 samples

2012-07-03 | E-GEOD-39091 | biostudies-arrayexpress

Expression data of A375 melanoma cells after DMSO or MLN4924 +/- Nutlin treatment for 26 hours

2012-07-04 | GSE39091 | GEO

Gene expression profiles of myeloma cells treated with NAE inhibitor

Project description:The transcriptional profile of the human multiple myeloma (MM) cell line MM.1S treated with MLN4924 vs control MM.1S cells was characterized by oligonucleotide microarray analysis, using the human U133 plus 2.0 Affymetrix GeneChip, according to previously described protocols for total RNA extraction and purification; cDNA synthesis; in vitro transcription reaction for production of biotin-labeled cRNA; hybridization of cRNA with U133plus2.0 Affymetrix gene chips; and scanning of image output files. Scanned image output files were analyzed using DNA-Chip Analyzer (dChip) (www.dchip.org), including conversion to DCP files, normalization and modeling. The gene expression profile of MM.1S cells for each time point of MLN4924 treatment was compared to the profile of control MM.1S cells. The NEDD8 activating enzyme (NAE) is upstream of the 20S proteasome in the ubiquitin/proteasome pathway and catalyzes the first step in the neddylation pathway. NEDD8 modification of cullins is required for ubiquitination of cullin-ring ligases (CRLs), which regulate degradation of a distinct subset of proteins. The more targeted impact of NAE on protein degradation prompted us to study MLN4924, an investigational NAE inhibitor, in preclinical multiple myeloma (MM) models. In vitro treatment with MLN4924 led to dose-dependent decrease of viability in a panel of human MM cell lines. In this analysis, we evaluated the molecular changes triggered in MM.1S myeloma cells by their in vitro treatment with MLN4924. The transcriptional profiles of each experimental condition were characterized by oligonucleotide microarray analysis, using the human U133 plus 2.0 Affymetrix GeneChip. The human multiple myeloma (MM) cells MM.1S were cultured in vitro in the presence or absence of the NEDD8 activating enzyme (NAE) inhibitor MLN4924 for 8, 16 or 24hrs. The gene expression profiles of drug treated cells were compared with the profiles of control MM.1S cells.

2012-05-01 | E-GEOD-33577 | biostudies-arrayexpress

Expression data of A375 melanoma cells after DMSO or MLN4924 treatment from 1 hour to 24 hour

Project description:Microarrays were used to determine the change in gene expression of genes involved in the CDT1/NAE pathway

2011-07-09 | GSE30531 | GEO

MLN4924 in chronic lymphocytic leukemia

Project description:CLL cells obtained from patients with CLL were treated with MLN4924 to determine whether NFkB transcription targets were affected by the drug. CLL cells were treated with 1 microM MLN4924 or vehicle control for 24 hours. Cells were collected by centrifugation and B-cell were purified using negative selection (B cell purification Kit, Multenyi Biotech). RNA was isolated and submitted for Gene expression analysis

2013-03-05 | E-GEOD-44864 | biostudies-arrayexpress

DNA damage Signaling Pathway PCR Array to profile the expression of human genes regulating in the DNA damage response (DDR) network

Project description:Human DNA Damage Signaling Pathway RT2 Profiler Array Kit (Qiagen, Valencia, CA) was used to profile the expression of key genes involved in the DDR network as per the manufacturerâs instructions. U937 cells were incubated with PXD-101 +/- MLN4924 for 16 h, after which the RT2 ProfilerTM DNA damage Signaling Pathway PCR Array was performed to profile the expression of 84 human genes involved in the DDR network.

2016-02-05 | E-GEOD-77560 | biostudies-arrayexpress

Analysis of A375 and A375 clones that acquired resistance to GSK2118436 after treatment with GSK2118436 (GSK436), GSK1120212 (GSK212), or the combination of GSK2118436 and GSK1120212 for 24 hour

Project description:In an effort to understand the mechanisms of acquired resistance to BRAF inhibitors, we isolated clones that acquired resistance to the BRAF inhibitor GSK2118436 derived from the A375 BRAF V600E mutant melanoma cell line. This resistance clones acquired mutations in NRAS and MEK1. One clones, 16R6-4, acquired two mutations in NRAS – Q61K and A146T. Proliferation and western blot analyses demonstrated that these clones were insensitive to single agent GSK2118436 or GSK1120212 (an allosteric MEK inhibitor) but were sensitive to the combination of GSK2118436 and GSK1120212. To further characterize this combination, global transcriptomic analysis was performed in A375 and 16R6-4 after 24 hour treatment with GSK2118436, GSK1120212 or the combination of GSK2118436 and GSK1120212. This data set was published in Molecular Cancer Therapeutics with the title “Combined inhibition of BRAF and MEK, BRAF and PI3K/mTOR, or MEK and PI3K/mTOR overcomes acquired resistance to the BRAF inhibitor GSK2118436, mediated by NRAS or MEK mutations” by Greger, J.G., et.al. A375 and 16R6-4 (an A375 derived GSK2118436 resistance clone) were treated for 24 hours with 0.1 micromolar GSK2118436, 1 micromolar GSK2118436, 0.01 micromolar GSK1120212, 0.1 micromolar GSK2118436 + 0.01 micromolar GSK1120212, or 1 micromolar GSK2118436 + 0.01 micromolar GSK1120212.

2012-02-01 | E-GEOD-35230 | biostudies-arrayexpress

Transcriptome data from human malanoma A375 cells stably expressing MAP4K5 shRNA.

Project description:MAP4K5 is serine/threonine protein kinase similar to yeast SPS1/STE20 kinase. MAP4K5 activates JNK in mammalian cells, which suggests a role in stress response. MAP4K5 is involved in immune functions. We used microarray to investigate genome-wide transcriptional change from MAP4K5 knockdown in A375 cells. Total RNA's from the A375 cells where MAP4K5 was stably knocked down by shRNA were analyzed. As a control, RNA's from A375 cells were also analyzed.

2014-09-18 | E-GEOD-61497 | biostudies-arrayexpress

Transcriptomic study of melanoma cell line A375 with miR-205 overexpression against controls

Project description:Transcriptomic identification of miR-205 target genes potentially involved in metastasis and survival of cutaneous malignant melanoma. We evaluated whole-genome mRNA expression profiling associated with different miR-205 expression levels in melanoma cells. Differential expression analysis, target prediction using TargetScan algorithm and functional analysis were performed to find those miR-205 associated genes involved in progression of melanoma.

2020-03-19 | E-MTAB-8202 | biostudies-arrayexpress

The COP9 signalosome reduces neuroinflammation and attenuates ischemic neuronal stress in organotypic brain slice culture model

Project description:In the context of studying the role of the COP9 signalosome (CSN) in neuroinflammation and ischemic neuronal damage, we studied the effect of the cullin NEDDylation state-modifying drugs MLN4924 and CSN5i-3 in BV2 microglial cells, an immortalized murine cell line featuring many of the characteristics of primary microglia. Owing to its potent inhibitory effect on the NEDDylation cascade, MLN4924 exhibits a CSN5-like anti-inflammatory activity. Csn5i-3 is a small molecule inhibitor that specifically binds to CSN5, while it resides in the CSN holocomplex and blocks its deNEDDylase activity, thus leading to an accumulation of NEDDylated cullins. We performed untargeted mass spectrometry-based proteomics of the cell lysates after treating BV2 cells with these drugs under basal culture stress conditions. The proteomic analysis revealed that MLN4924 and CSN5i-3 substantially altered the microglial proteome.

2023-10-24 | PXD044650 | Pride

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