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Pinning Control for the p53-Mdm2 Network Dynamics Regulated by p14ARF

Oscar J Suarez1, Carlos J Vega1, Edgar N Sanchez1

  • 1Electrical Engineering Department, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Guadalajara, Mexico.

Frontiers in Physiology
|September 28, 2020
PubMed

Insights

This study introduces a control strategy for the p53-Mdm2 gene network using pinning control. The method successfully models and regulates cellular stress responses, including gamma-radiation effects and p53 expression.

Area of Science:

  • Systems biology
  • Gene regulatory network analysis
  • Computational modeling

Background:

  • The p53-Mdm2 network is crucial for cellular response to genotoxic stress and cancer prevention.
  • This network's regulation is activated by various signaling pathways under cellular stress.
  • p14ARF plays a role in modulating the p53-Mdm2 network.

Purpose of the Study:

  • To develop a control strategy for the p53-Mdm2 gene network regulated by p14ARF.
  • To apply pinning control techniques to a small number of critical nodes within the network.
  • To model and control gene regulatory network dynamics in response to cellular stress.

Main Methods:

  • Utilized pinning control by applying local feedback controllers to strategically selected nodes.
  • Selected pinned nodes based on topological hierarchy, connectivity, and biological function.
  • Employed a computational algorithm to simulate and analyze network behavior under different conditions.

Main Results:

  • Successfully recovered the oscillatory pattern of the p53-Mdm2 network under gamma-radiation.
  • Achieved controlled increase in p53 expression levels.
  • Demonstrated the effectiveness of pinning control on p14ARF to manage Mdm2-mediated p53 degradation.

Conclusions:

  • The developed pinning control strategy offers a novel approach to understanding and managing cellular stress responses.
  • This computational method enables modeling and control of gene regulatory network dynamics in distinct biological scenarios.
  • The technique shows promise for addressing carcinogenic behaviors driven by p53 degradation.
Keywords:
Mdm2computational modelingp14ARFp53pinning control

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