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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

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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]

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