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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
The role of time delays in P53 gene regulatory network stimulated by growth factor
Chang Yong Dai1, Hai Hong Liu1, Hai Hong Liu1,2
1Department of Mathematics, Yunnan Normal University, Kunming, 650500, China.
Abstract:
In this paper, a delayed mathematical model for the P53-Mdm2 network is developed. The P53-Mdm2 network we study is triggered by growth factor instead of DNA damage and the amount of DNA damage is regarded as zero. We study the influences of time delays, growth factor and other important chemical reaction rates on the dynamic behaviors in the system. It is shown that the time delay is a critical factor and its length determines the period, amplitude and stability of the P53 oscillation. Furthermore, as for some important chemical reaction rates, we also obtain some interesting results through numerical simulation. Especially, S (growth factor), k3 (rate constant for Mdm2 dephosphorylation), k10 (basal expression of PTEN) and k14 (Rate constant for PTEN-induced Akt dephosphorylation) could undermine the dynamic behavior of the system in different degree. These findings are expected to understand the mechanisms of action of several carcinogenic and tumor suppressor factors in humans under normal conditions.
Insights
Time delays critically influence the P53-Mdm2 network
Area of Science:
- Mathematical biology
- Systems biology
- Biochemical dynamics
Background:
- The P53-Mdm2 network is crucial for cellular responses.
- This study focuses on growth factor-induced signaling, not DNA damage.
- Understanding network dynamics is key to cancer research.
Purpose of the Study:
- To develop a delayed mathematical model for the P53-Mdm2 network.
- To investigate the impact of time delays and reaction rates on system dynamics.
- To analyze the role of growth factors and specific rate constants.
Main Methods:
- Development of a delayed mathematical model.
- Numerical simulations to analyze dynamic behaviors.
- Sensitivity analysis of key parameters.
Main Results:
- Time delay is a critical factor affecting P53 oscillation period, amplitude, and stability.
- Growth factor (S) and rate constants (k3, k10, k14) significantly impact system dynamics.
- Specific rate constants identified as potentially undermining network behavior.
Conclusions:
- Time delays are essential for regulating P53 oscillations in this network.
- Key reaction rates, including those for Mdm2 dephosphorylation and PTEN/Akt pathways, modulate network function.
- Findings offer insights into the mechanisms of carcinogenic and tumor suppressor factors.
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