Pinning Control for the p53-Mdm2 Network Dynamics Regulated by p14ARF
p53 regulates the cellular response to genotoxic damage and prevents carcinogenic events. Theoretical and experimental studies state that the p53-Mdm2 network constitutes the core module of regulatory interactions activated by cellular stress induced by a variety of signaling pathways. In this paper...
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doaj-ea6d1324c80e4c62ba429c548dd5d8a42020-11-25T03:48:02ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-08-011110.3389/fphys.2020.00976492386Pinning Control for the p53-Mdm2 Network Dynamics Regulated by p14ARFOscar J. Suarez0Carlos J. Vega1Edgar N. Sanchez2Ana E. González-Santiago3Otoniel Rodríguez-Jorge4Alma Y. Alanis5Guanrong Chen6Esteban A. Hernandez-Vargas7Electrical Engineering Department, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Guadalajara, MexicoElectrical Engineering Department, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Guadalajara, MexicoElectrical Engineering Department, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Guadalajara, MexicoBiomedical Sciences Department, Centro de Investigación Multidisciplinario en Salud, Universidad de Guadalajara, Tonalá, MexicoBiochemistry and Molecular Biology Department, Instituto de Investigaciones Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, MexicoComputer Sciences Department, Universidad de Guadalajara, Guadalajara, MexicoElectrical Engineering Department, City University of Hong Kong, Hong Kong, ChinaFrankfurt Institute for Advanced Studies, Frankfurt, Germanyp53 regulates the cellular response to genotoxic damage and prevents carcinogenic events. Theoretical and experimental studies state that the p53-Mdm2 network constitutes the core module of regulatory interactions activated by cellular stress induced by a variety of signaling pathways. In this paper, a strategy to control the p53-Mdm2 network regulated by p14ARF is developed, based on the pinning control technique, which consists into applying local feedback controllers to a small number of nodes (pinned ones) in the network. Pinned nodes are selected on the basis of their importance level in a topological hierarchy, their degree of connectivity within the network, and the biological role they perform. In this paper, two cases are considered. For the first case, the oscillatory pattern under gamma-radiation is recovered; afterward, as the second case, increased expression of p53 level is taken into account. For both cases, the control law is applied to p14ARF (pinned node based on a virtual leader methodology), and overexpressed Mdm2-mediated p53 degradation condition is considered as carcinogenic initial behavior. The approach in this paper uses a computational algorithm, which opens an alternative path to understand the cellular responses to stress, doing it possible to model and control the gene regulatory network dynamics in two different biological contexts. As the main result of the proposed control technique, the two mentioned desired behaviors are obtained.https://www.frontiersin.org/article/10.3389/fphys.2020.00976/fullp53Mdm2p14ARFpinning controlcomputational modeling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Oscar J. Suarez Carlos J. Vega Edgar N. Sanchez Ana E. González-Santiago Otoniel Rodríguez-Jorge Alma Y. Alanis Guanrong Chen Esteban A. Hernandez-Vargas |
spellingShingle |
Oscar J. Suarez Carlos J. Vega Edgar N. Sanchez Ana E. González-Santiago Otoniel Rodríguez-Jorge Alma Y. Alanis Guanrong Chen Esteban A. Hernandez-Vargas Pinning Control for the p53-Mdm2 Network Dynamics Regulated by p14ARF Frontiers in Physiology p53 Mdm2 p14ARF pinning control computational modeling |
author_facet |
Oscar J. Suarez Carlos J. Vega Edgar N. Sanchez Ana E. González-Santiago Otoniel Rodríguez-Jorge Alma Y. Alanis Guanrong Chen Esteban A. Hernandez-Vargas |
author_sort |
Oscar J. Suarez |
title |
Pinning Control for the p53-Mdm2 Network Dynamics Regulated by p14ARF |
title_short |
Pinning Control for the p53-Mdm2 Network Dynamics Regulated by p14ARF |
title_full |
Pinning Control for the p53-Mdm2 Network Dynamics Regulated by p14ARF |
title_fullStr |
Pinning Control for the p53-Mdm2 Network Dynamics Regulated by p14ARF |
title_full_unstemmed |
Pinning Control for the p53-Mdm2 Network Dynamics Regulated by p14ARF |
title_sort |
pinning control for the p53-mdm2 network dynamics regulated by p14arf |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2020-08-01 |
description |
p53 regulates the cellular response to genotoxic damage and prevents carcinogenic events. Theoretical and experimental studies state that the p53-Mdm2 network constitutes the core module of regulatory interactions activated by cellular stress induced by a variety of signaling pathways. In this paper, a strategy to control the p53-Mdm2 network regulated by p14ARF is developed, based on the pinning control technique, which consists into applying local feedback controllers to a small number of nodes (pinned ones) in the network. Pinned nodes are selected on the basis of their importance level in a topological hierarchy, their degree of connectivity within the network, and the biological role they perform. In this paper, two cases are considered. For the first case, the oscillatory pattern under gamma-radiation is recovered; afterward, as the second case, increased expression of p53 level is taken into account. For both cases, the control law is applied to p14ARF (pinned node based on a virtual leader methodology), and overexpressed Mdm2-mediated p53 degradation condition is considered as carcinogenic initial behavior. The approach in this paper uses a computational algorithm, which opens an alternative path to understand the cellular responses to stress, doing it possible to model and control the gene regulatory network dynamics in two different biological contexts. As the main result of the proposed control technique, the two mentioned desired behaviors are obtained. |
topic |
p53 Mdm2 p14ARF pinning control computational modeling |
url |
https://www.frontiersin.org/article/10.3389/fphys.2020.00976/full |
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