Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA340264 | ENA |
REPOSITORIES: ENA
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Project description:The goal of the study is to identify p53 target genes specific to macrophages using the p53 stabilizer, Nutlin-3.
2014-05-21 | GSE43596 | GEO
Project description:The goal of the study is to identify p53 target genes specific to macrophages using the p53 stabilizer, Nutlin-3. Macrophages were differentiated x-vivo from monocytes obtained from healthy volunteers either left untreated or treated for 2 hours with 100 ng/mL of lipopolysaccharide (LPS), 0.1%v/v of DMSO (vehicle control for Nutlin-3) or 10 micromolar Nutlin-3. Three replicates were included for each treatment group.
2014-05-21 | E-GEOD-43596 | biostudies-arrayexpress
Project description:Background: p53 plays a key role in determining the clinical features of B cell chronic lymphocytic leukemia (CLL). Disruption of p53 by point mutations, deletion at 17p13, or both, occurs in a fraction of cases at diagnosis and predicts poor survival and chemorefractoriness. In cells with functional p53, p53 activity is inhibited through interaction with MDM2. In fact, p53 can be activated upon exposure of cells to inhibitors of p53/MDM2 interaction, like Nutlins. Exposure of CLL cells to Nutlin-3 is effective in raising the levels of p53 protein with subsequent induction of cell cycle arrest and/or apoptosis, independently of the most relevant prognostic markers. Specific gene-sets and GEP were documented to be associated with response or resistance to Nutlin-3 exposure in p53(wt) or p53(del/mut) CLL. These findings may help to identify novel molecular targets for CLL therapy. Aim: to analyze the gene expression profile (GEP) induced by Nutlin-3 exposure in primary CLL cells from p53(wt) and p53(del/mut) cases. Methods: purified cells from 24 PB CLL samples, all characterized for IGHV mutational status, CD38 and ZAP-70 and p53 mutations (16 p53(wt) CLL, 8 p53(del/mut) CLL of which 6 with del17p13 and p53 mutations, 1 with del17p13 alone, and 1 with p53 mutations alone), were exposed to 10 uM Nutlin-3 for 24 hours. GEP was performed using a dual labelling strategy; the differential expression of the below reported genes were validated by quantitative real-time PCR. specific gene-sets and GEP were documented to be associated with response or resistance to Nutlin-3 exposure in p53(wt) or p53(del/mut) CLL. These findings may help to identify novel molecular targets for CLL therapy.
2009-11-11 | GSE18971 | GEO
Project description:Gene-expression in siRNA treated U2OS and hTERT-RPE1 cells showed that CASP8AP2, NPAT and HINFP do not regulate expression of each other, and do not have any common target genes, except histones. Most histone genes are downregulated in U2OS cells following loss of CASP8AP2, NPAT or HINFP. In normal cells, highly-expressed histone genes were downregulated, albeit less than in tumor cells following loss of CASP8AP2. The p53 target genes were upregulated relatively late, clearly after the changes in expression of histone genes were observed. U2OS and hTERT-RPE1 cells were treated with CASP8AP2, NPAT, HINFP or control siRNA in duplicates or triplicates and collected for RNA purification on 1st, 2nd and 3d days.
2016-09-01 | E-GEOD-69148 | biostudies-arrayexpress
Project description:We have used chromatin immune-precipitation with parallel sequencing (ChIP-Seq) technology to identify genome-wide p53 binding in human lymphoblastoid cell lines treated with a MDM2 inhibitor nutlin-3 ChIP-Seq analysis of p53 binding sites in human lymphoblastoid cells treated with nutlin-3 or vehicle
2013-10-23 | E-GEOD-46992 | biostudies-arrayexpress
Project description:The tumor suppressor p53 prevents cancer development through regulation of dozens of target genes with diverse biological functions. Numerous p53 target genes have been identified to date, whereas the dynamics and function of the regulatory network centered on p53 have not yet been fully elucidated. To identify novel p53 target genes, we performed RNA sequencing and differential expression analysis on MCF7 cells treated with DMSO or Nutlin-3, a nongenotoxic small molecule that activates p53 through disruption of p53-MDM2 interaction. Among the top 15 differentially expressed genes, we found a potent transcriptional target of p53.
2024-03-26 | GSE254303 | GEO
Project description:We investigated the genes that were most strongly activated by p53 in this immortalized human cell line following treatment with the MDM2 inhibitor nutlin-3a. To identify genes that were activated by p53, we comparatively analyzed parental cells and isogenic derivatives. Wild type, p53-knockout and cells harboring a heterozygous p53 A276P mutation were assessed.
2023-05-01 | GSE229160 | GEO
Project description:Several genome-wide transcriptome analyses that focused on p53-induced cellular responses in many cellular contexts have continued to expand the already vast p53-regulated transcriptional networks. To investigate post-transcriptional controls as an additional dimension of p53-directed gene expression responses we performed translatome analysis by polysomal profiling on MCF7 cells treated with Doxorubicin and Nutlin-3a. A comparison between the transcriptome and the translatome revealed a large number of uncoupled genes, whose transcription changes did not correlate with translation changes. Overall, we establish p53 as a master regulator of translational control and identify many p53 target genes affecting translation that can contribute to p53-dependent cellular responses. Keywords: p53, transcriptome, translatome, polysomal RNA, subpolysomal RNA, uncoupling, Doxorubicin, Nutlin-3a
2014-04-17 | GSE50650 | GEO
Project description:Several genome-wide transcriptome analyses that focused on p53-induced cellular responses in many cellular contexts have continued to expand the already vast p53-regulated transcriptional networks. To investigate post-transcriptional controls as an additional dimension of p53-directed gene expression responses we performed translatome analysis by polysomal profiling on MCF7 cells treated with Doxorubicin and Nutlin-3a. A comparison between the transcriptome and the translatome revealed a large number of uncoupled genes, whose transcription changes did not correlate with translation changes. Overall, we establish p53 as a master regulator of translational control and identify many p53 target genes affecting translation that can contribute to p53-dependent cellular responses. Keywords: p53, transcriptome, translatome, polysomal RNA, subpolysomal RNA, uncoupling, Doxorubicin, Nutlin-3a Total RNA (tot) was extracted from MCF7 vector cells after 16h of treatment with Doxorubicin (1.5uM) and Nutlin-3a (10uM) or DMSO (solvent, as control treatment). Polysomal profiling was performed after the same conditions. We collected all subpolysomal mRNA fractions (sub) and the polysomal ones (pol) after sucrose gradient fractionation of cytoplasmic lysates to analyze separately mRNAs that are not actively translated from those that are considered in active translation, respectively. Experiments were performed in three biological replicates.
2014-04-17 | E-GEOD-50650 | biostudies-arrayexpress
Project description:The effects of diverse stresses on promoter selectivity and transcription regulation by the tumor suppressor p53 are poorly understood. We have taken a comprehensive approach to characterizing the human p53 network that includes p53 levels, binding, expression and chromatin changes under diverse stresses. Human osteosarcoma U2OS cells treated with anti-cancer drugs Doxorubicin or Nutlin-3 led to strikingly different p53 gene binding patterns based on ChIP-seq experiments. While two contiguous RRRCWWGYYY decamers is the consensus binding motif, p53 can bind a single decamer and function in vivo. Although the number of sites bound by p53 was 6-times greater for Nutlin-3 than Doxorubicin, expression changes induced by Nutlin-3 were much less dramatic compared to Doxorubicin. Unexpectedly, the solvent DMSO alone induced p53 binding to many sites common to Doxorubicin; however, this binding had no effect on target gene expression. Together, these data imply a two-stage mechanism for p53 transactivation where p53 binding only constitutes the first stage. Furthermore, both p53 binding and transactivation were associated with increased active histone modification H3K4me3. We discovered 149 putative new p53 target genes including several that are relevant to tumor suppression, revealing potential new targets for cancer therapy and expanding our understanding of the p53 regulatory network. Gene expression analysis (using Affymetrix Human Genome U133 Plus 2.0 GeneChip® arrays) of the p53 response in U2OS cells treated with either Doxorubicin or Nutlin-3, relative to their controls No Treatment and DMSO, respectively.
2013-07-01 | E-GEOD-46493 | biostudies-arrayexpress