Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Konrath2020_p53_signaling_model

ABSTRACT: The ODE model is based on Batchelor et al., Mol. Syst. Biol. 7 (2011) and was extended by introducing explicit descriptions of the transcription and translation processes of Mdm2 mRNA and Wip1 mRNA. To capture the heterogeneous single cell dynamics of p53 with an ODE model, we clustered the time courses measured by single cell time lapse microscopy into ten subpopulations and created subpopulation models (labelled "a" to "j"). By fitting the subpopulation models to the clustered time course data, we developed to our knowledge the first quantitative p53 model reproducing heterogeneous dynamics of p53.

SUBMITTER: Fabian Konrath

PROVIDER: MODEL2004300002 | BioModels | 2020-05-07

REPOSITORIES: BioModels

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	MODEL2004300002?filename=Konrath2020_p53_subpopulation_a_l2v4.xml	Xml
	MODEL2004300002?filename=Konrath2020_p53_subpopulation_b_l2v4.xml	Xml
	MODEL2004300002?filename=Konrath2020_p53_subpopulation_c_l2v4.xml	Xml
	MODEL2004300002?filename=Konrath2020_p53_subpopulation_d_l2v4.xml	Xml
	MODEL2004300002?filename=Konrath2020_p53_subpopulation_e_l2v4.xml	Xml

Items per page:

1 - 5 of 14

Publications

A systematic approach to decipher crosstalk in the p53 signaling pathway using single cell dynamics.

Konrath Fabian F Mittermeier Anna A Cristiano Elena E Wolf Jana J Loewer Alexander A

PLoS computational biology 20200626 6

The transcription factors NF-κB and p53 are key regulators in the genotoxic stress response and are critical for tumor development. Although there is ample evidence for interactions between both networks, a comprehensive understanding of the crosstalk is lacking. Here, we developed a systematic approach to identify potential interactions between the pathways. We perturbed NF-κB signaling by inhibiting IKK2, a critical regulator of NF-κB activity, and monitored the altered response of p53 to geno ...[more]

PMID: 32589666

Similar Datasets

Quantifying Cell Heterogeneity and Subpopulations Using Single Cell Metabolomics

Project description:We combined the Single-probe single cell MS(SCMS) experimental technique with a bioinformatics software package, SinCHet-MS (Single Cell Heterogeneity for Mass Spectrometry), to characterize changes of tumor heterogeneity, quantify cell subpopulations, and prioritize the metabolite biomarkers of each subpopulation.

2023-06-15 | MSV000092178 | MassIVE

A circular RNA from the MDM2 locus regulates proliferation by suppressing basal p53 levels

Project description:Circular RNAs (circRNAs) are a class of noncoding RNAs produced by a non-canonical form of alternative splicing called back-splicing. To investigate a potential role of circRNAs in the p53 pathway, we analyzed RNA-seq data from colorectal cancer cell lines (HCT116, RKO and SW48) in the presence or absence of DNA damage. Surprisingly, unlike the strong p53-dependent induction of hundreds of p53-induced mRNAs, only a few circRNAs were induced from the p53-induced genes. Circ-MDM2, an annotated circRNA from the MDM2 locus, was one of the handful of circRNAs that originated from a p53-induced gene. Given the central role of MDM2 in suppressing p53 protein levels and p53 activity, we investigated the function of circ-MDM2. Knocking down circ-MDM2 with siRNAs that targeted the circ-MDM2 junction and had no effect on linear MDM2 mRNA, resulted in increased basal p53 levels and growth defects in vitro and in vivo. Consistent with these results, transcriptome profiling showed increased expression of several direct p53 targets, reduced Rb phosphorylation and defects in G1-S progression upon silencing circ-MDM2. Our results reveal the role of a novel circRNA by which the MDM2 locus suppresses p53 levels and cell cycle progression.

2020-03-04 | GSE138016 | GEO

Nanostring microRNA microarry analysis of p53 and Mdm2 knockout mouse hearts compared to vehicle-injected negative controls

Project description:Adult cardiomyocytes (CM) are terminally differentiated cells with minimal regenerative capacity, making cardiac tissue particularly vulnerable to injury. Thus, defining the roadblocks responsible for adult CM cell cycle arrest lies at the core of developing therapies to regenerate myocyte loss following injurious events such as myocardial infarction. We have previously shown that inactivating the p53/Mdm2 tumor suppressor circuitry, specifically in the heart (using the Cre-loxP recombination system of bacteriophage P1), can allow differentiated CMs to regain proliferative capacity, through an upregulation of factors involved in cell cycle re-entry. These factors are repressed in quiescent CMs, in part through the action of microRNAs (miRNAs). Notably, knockout of either p53 or Mdm2 individually was insufficient to promote CM proliferation. Therefore, we hypothesized that inactivation of p53/Mdm2-regulated miRNAs could promote the expression of cell cycle activators and induce proliferation of adult murine CMs. To identify miRNAs regulated by both p53 and Mdm2, total miRNA expression profiles from cardiac specific p53/Mdm2 double knockout (DKO) mouse hearts were compared with those from cardiac-specific single knockouts (p53KO and Mdm2KO), and vehicle-injected controls using the Nanostring nCounter mouse miRNA expression assay. This revealed a profile of 11 significantly downregulated miRNAs in the proliferative DKO hearts (versus vehicle-injected control), that were enriched for mRNA targets involved in cell cycle regulation. In vitro studies have demonstrated that knockdown of these 11 miRNAs in neonatal rat cardiomyocytes can increase the occurrence of cytokinetic events. Ultimately, we aim to inject antagomirs targeting these miRNAs into animals post-myocardial infarction to determine the effect of p53/Mdm2-regulated miRNAs on heart function and CM proliferation in vivo.

2017-03-22 | E-MTAB-5531 | biostudies-arrayexpress

GNPS - Quantifying Cell Heterogeneity and Subpopulations Using Single Cell Metabolomics

2023-06-15 | MSV000092178 | GNPS

Total RNA-seq from HCT116, MCF7 and SJSA cell lines treated with DMSO and Nutlin

Project description:To determine effects of p53 activation on steady-state mRNA levels, we performed RNA-seq analysis of colorectal carcinoma cell line HCT116 (p53+/+ and p53 -/-), breast carcinoma line MCF7, and osteosarcoma line SJSA treated with MDM2 inhibitor Nutlin.

2017-08-22 | GSE86221 | GEO

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [RNA-Seq]

Project description:The Mdm2 oncoprotein ubiquitinates and antagonizes p53 but may also carry out p53-independent functions. Here we report that Mdm2 is required for the efficient generation of induced pluripotent stem cells (iPSCs) from murine embryonic fibroblasts, in the absence of p53. Similarly, Mdm2 depletion in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the Mdm2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. Mdm2 physically associated with EZH2 on chromatin, enhancing the trimethylation of Histone 3 at lysine 27 and the ubiquitination of Histone 2A at lysine 119 (H2AK119) at its target genes. Removing Mdm2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell proliferation. In conclusion, Mdm2 supports the Polycomb-mediated repression of lineage specific genes independent of p53. Expression profiling by high throughput sequencing of p53 ko MEFs, p53Mdm2 ko MEFs, p53ko Mdm2 C462A ki MEFs.

2015-12-31 | E-GEOD-73176 | biostudies-arrayexpress

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [HCT116 microarray]

2015-12-31 | E-GEOD-73294 | biostudies-arrayexpress

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [ChIP-Seq]

2015-12-31 | E-GEOD-73293 | biostudies-arrayexpress

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [hMSC microarray]

Project description:The Mdm2 oncoprotein ubiquitinates and antagonizes p53 but may also carry out p53-independent functions. Here we report that Mdm2 is required for the efficient generation of induced pluripotent stem cells (iPSCs) from murine embryonic fibroblasts, in the absence of p53. Similarly, Mdm2 depletion in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the Mdm2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. Mdm2 physically associated with EZH2 on chromatin, enhancing the trimethylation of Histone 3 at lysine 27 and the ubiquitination of Histone 2A at lysine 119 (H2AK119) at its target genes. Removing Mdm2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell proliferation. In conclusion, Mdm2 supports the Polycomb-mediated repression of lineage specific genes independent of p53. microarray analysis in osteoblasts differentiated from human mesenchymal stem cells after siRNA kd

2015-12-31 | E-GEOD-73601 | biostudies-arrayexpress

Genome-wide maps of chromatin binding site for Mdm2.

Project description:The MDM2 oncoprotein is an essential component of the p53 pathway. Although MDM2 has been widely described as a major negative regulator of the p53 tumor suppressor, growing evidences support the notion that Mdm2 functions are also mediated through p53 independent mechanisms. We found that MDM2 is recruited on chromatin. By ChIP-Seq (using MDM2 antibody) of H1299 cells exhibiting MDM2 recruitment on chromatin, we identified at the whole genome level MDM2 binding sites. Both input and IPped-DNA were exhaustively sequenced and mapped on human genome

2016-06-09 | GSE64439 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data