Genome-wide analysis of p53 binding protein
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE51268 | GEO | 2014/04/01
SECONDARY ACCESSION(S): PRJNA222272
REPOSITORIES: GEO
Similar Datasets
Project description:Tumor suppressor p53 regulates various role in the cell including cell cycle arrest, DNA repair and apoptosis. Current research achieved to investigate p53 target genes in human osteosarcoma cell line-SaOS2 cell. Examination of p53 binding protein by transfecting flag-tagged wild type p53 into SaOS2 cells.
2014-04-01 | E-GEOD-51268 | biostudies-arrayexpress
Project description:The p53 family consists of three members, p53, p73, and p63. These proteins share a high degree of amino-acid sequence similarity and major functional domains. The p53 gene, the first member of the family to be identified, is the most frequent target gene for genetic alterations in human cancers. In contrast, p73 and p63 are mainly involved in normal development and differentiation. These differences among the p53 family are likely to depend on activation or repression of different sets of target genes. In this study, to identify targets specifically regulated by p73, we performed microarray analysis and compared expression patterns in a human steosarcoma cell line Saos-2 infected separately with p53 and TAp73beta expressing adenovirus. Experiment Overall Design: Saos2 osteosarcoma cells were infected with p53, TAp73beta expressing or control adenovirus for 24 h and then harvested.
2008-11-15 | E-GEOD-13504 | biostudies-arrayexpress
Project description:After DNA damage, cells activate p53, a tumor suppressor gene, and select a cell fate (e.g., DNA repair, cell cycle arrest, or apoptosis). Recently, a p53 oscillatory behavior was observed following DNA damage. However, the relationship between this p53 oscillation and cell-fate selection is unclear. Here, we present a novel model of the DNA damage signaling pathway that includes p53 and whole cell cycle regulation and explore the relationship between p53 oscillation and cell fate selection. The simulation run without DNA damage qualitatively realized experimentally observed data from several cell cycle regulators, indicating that our model was biologically appropriate. Moreover, the comprehensive sensitivity analysis for the proposed model was implemented by changing the values of all kinetic parameters, which revealed that the cell cycle regulation system based on the proposed model has robustness on a fluctuation of reaction rate in each process. Simulations run with four different intensities of DNA damage, i.e. Low-damage, Medium-damage, High-damage, and Excess-damage, realized cell cycle arrest in all cases. Low-damage, Medium-damage, High-damage, and Excess-damage corresponded to the DNA damage caused by 100, 200, 400, and 800 J/m(2) doses of UV-irradiation, respectively, based on expression of p21, which plays a crucial role in cell cycle arrest. In simulations run with High-damage and Excess-damage, the length of the cell cycle arrest was shortened despite the severe DNA damage, and p53 began to oscillate. Cells initiated apoptosis and were killed at 400 and 800 J/m(2) doses of UV-irradiation, corresponding to High-damage and Excess-damage, respectively. Therefore, our model indicated that the oscillatory mode of p53 profoundly affects cell fate selection.
2024-09-02 | BIOMD0000000939 | BioModels
Project description:Our compound (PRIMA) selectively kills tumor cells expressing mutant p53. Here in our study we decided to investigate the impact of our compound on the transcriptome of Saos2 cells lacking p53.
2009-04-15 | GSE15367 | GEO
Project description:Our compound (PRIMA) selectively kills tumor cells expressing mutant p53. Here in our study we decided to investigate the impact of our compound on the transcriptome of p53 mutant-expressing cells, Saos2-His273.
2009-04-15 | GSE15368 | GEO
Project description:In response to stress, the p53 tumor suppressor induces arrest or apoptosis by transcriptionally regulating genes that mediate these processes. It has been proposed that the levels of p53 can influence the choice between these different outcomes, but the mechanisms involved are not clear. To gain mechanistic understanding of this p53-dependent cell fate decision, we generated a p53 inducible system that allowed tight regulation of p53 expression in human mammary epithelial cells. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Using microarray and chromatin immunoprecipitation analysis, we showed that low and high levels of p53 bind to and activate the same set of pro arrest and pro apoptotic target genes, induced to lower and higher levels, respectively. We propose that the cell fate decision between arrest and apoptosis in these cells is determined by a higher threshold required for p53 dependent apoptosis. We suggest that high level p53 activation is crucial in order to achieve maximum efficacy of p53 targeted cancer therapies.
2011-07-19 | E-GEOD-30753 | biostudies-arrayexpress
Project description:p63, like its homologue, the tumor suppressor p53, is also able to induce apoptosis in several cancer cell types. p53 family proteins are composed of three characteristic domains which are: 1) an N-terminal transactivation domain (TAD); 2) a central DNA-binding domain (DBD); and 3) an oligomerization domain (OD). In this study, we constructed recombinant adenoviruses containing hybrid genes composed of fragments of p53 and TAp63γ genes by connecting coding sequences of their three functional domains. The potency of tumor growth suppression of these hybrid molecules was evaluated using in vitro and in vivo models. One of the p53-p63 hybrid molecules, p63-53O, was observed to be the most potent activator of human cancer cells to apoptosis when compared to the p53, TAp63γ or several alternative p53-p63 hybrid molecules. p63-53O hybrid is composed of TAD and DBD of TAp63γ and OD of p53. In an effort to identify specific targets regulated by pro-apoptotic hybrid p63-53O, we next performed Affymetrix Genechip analysis and compared expression patterns in a human osteosarcoma cell line Saos-2 transfected separately with Ad-p53, Ad-TAp63γ and Ad-p63-53O. Saos-2 osteosarcoma cells were either transduced with adenoviral vectors expressing p53, TAp63gamma, p53-p63 hybrid (p63-53O), or GFP. After 24 hours, mRNA was isolated and analyzed by hybridization to Affymetrix HG-U133 plus 2 arrays.
2012-02-04 | E-GEOD-35512 | biostudies-arrayexpress
Project description:The goal is to profile RUNX2 and CBFB binding sites in an osteosarcoma cell line, SAOS2.
2017-02-11 | GSE76937 | GEO
Project description:Exposure to genotoxic stress promotes cell-cycle arrest and DNA repair or apoptosis. These “life” or “death” cell fate decisions often rely on the activity of the tumor suppressor gene p53. Therefore, how p53 activity is precisely regulated is essential to maintain tissue homeostasis and to prevent cancer development. Here we demonstrate that Drosophila p53 pro-apoptotic activity is regulated by the G2/M kinase Cdk1. We find that cell cycle arrested or endocycle-induced cells are refractory to ionizing radiation induced apoptosis. We show that the p53 protein is not able to bind to the p53 responding elements of the pro-apoptotic genes and to activate their expression in experimentally arrested cells. Our results indicate that p53 genetically and physically interacts with Cdk1 and that p53 pro-apoptotic role is regulated by the cell cycle status of the cell. We propose a model in which cell cycle progression and p53 pro-apoptotic activity are molecularly connected to coordinate the appropriate response after DNA damage.
2021-11-26 | GSE169668 | GEO
Project description:The p53 transcription factor is a regulator of key cellular processes including DNA repair, cell cycle arrest, and apoptosis. In this theoretical study, we investigate how the complex circuitry of the p53 network allows for stochastic yet unambiguous cell fate decision-making. The proposed Markov chain model consists of the regulatory core and two subordinated bistable modules responsible for cell cycle arrest and apoptosis. The regulatory core is controlled by two negative feedback loops (regulated by Mdm2 and Wip1) responsible for oscillations, and two antagonistic positive feedback loops (regulated by phosphatases Wip1 and PTEN) responsible for bistability. By means of bifurcation analysis of the deterministic approximation we capture the recurrent solutions (i.e., steady states and limit cycles) that delineate temporal responses of the stochastic system. Direct switching from the limit-cycle oscillations to the "apoptotic" steady state is enabled by the existence of a subcritical Neimark-Sacker bifurcation in which the limit cycle loses its stability by merging with an unstable invariant torus. Our analysis provides an explanation why cancer cell lines known to have vastly diverse expression levels of Wip1 and PTEN exhibit a broad spectrum of responses to DNA damage: from a fast transition to a high level of p53 killer (a p53 phosphoform which promotes commitment to apoptosis) in cells characterized by high PTEN and low Wip1 levels to long-lasting p53 level oscillations in cells having PTEN promoter methylated (as in, e.g., MCF-7 cell line).
2024-09-02 | BIOMD0000000943 | BioModels