Математическое моделирование функционирования сигнального пути p53 при повреждении ДНК.I. Модель активации системы p53 - Mdm2 - Wip

Translated title of the contribution: Mathematical modelling for the functioning of the p53 signaling pathway following DNA damage. I. The model of activation of the p53-Mdm2-Wipl system

Voropaeva F. Olga, Gavrilova S. Ksenia

Research output: Contribution to journalArticlepeer-review

Abstract

In the context of the survival and death of cells with DNA damage, a special role is assigned to the p53 protein. The management of p53 and its inhibitors can provide a protective effect in a wide range of degenerative diseases, such as cancer, infarctions, and dementia. Therefore, there are increased requirements for mathematical models designed to study the mechanism of functioning of the p53 signaling pathway. Our work is devoted to the study of the properties of the well-known mathematical model of the dynamics of the p53-Mdm2-Wipl system under various influences leading to DNA damage. A simple modification of the model is proposed. The main attention is paid to the analysis of the sensitivity and qualitative properties of solutions, as well as the validation of the model before and after its modification. In numerical experiments, it was found that within the framework of the accepted models, the stationary state of the p53-Mdm2-Wipl system can be unstable to negligible changes in the initial conditions, so that the system can function under the same parameter values according to the bifurcation scenario with a doubling of the period. The mathematical conditions under which the multiplicity of solutions and complex dynamic modes were detected allow for a biological interpretation as a reflection of the variability in the response of the p53 protein pathway to the damage signal. The range of applicability of the models was compared using the example of a well-known laboratory experiment, in which the most complete set of observed in vitro and in vivo states of the p53-Wipl system was demonstrated when irradiating cancer cells with wild-type p53. It is shown that the simplest modification of the original model significantly expands the scope of its applicability, allows describing the transition from normal to critical states of the system associated with known degenerative diseases. Thus, the modified model is a more effective tool for numerical analysis of a wide range of states of the p53-Mdm2-Wipl system.

Translated title of the contributionMathematical modelling for the functioning of the p53 signaling pathway following DNA damage. I. The model of activation of the p53-Mdm2-Wipl system
Original languageRussian
Article number3
Pages (from-to)33-53
Number of pages21
JournalJournal of Computational Technologies
Volume26
Issue number6
DOIs
Publication statusPublished - 2021

OECD FOS+WOS

  • 1.01 MATHEMATICS

State classification of scientific and technological information

  • 27 MATHEMATICS

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