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The Dynamics of Stress p53-Mdm2 Network Regulated by p300 and HDAC1

A. Arora,S. Gera,T. Maheshwari,Dhwani Raghav,Md. Jahoor Alam,K. R,Brojen Singh,S. Agarwal

Published 2013 in PLoS ONE

ABSTRACT

We construct a stress p53-Mdm2-p300-HDAC1 regulatory network that is activated and stabilised by two regulatory proteins, p300 and HDAC1. Different activation levels of observed due to these regulators during stress condition have been investigated using a deterministic as well as a stochastic approach to understand how the cell responds during stress conditions. We found that these regulators help in adjusting p53 to different conditions as identified by various oscillatory states, namely fixed point oscillations, damped oscillations and sustain oscillations. On assessing the impact of p300 on p53-Mdm2 network we identified three states: first stabilised or normal condition where the impact of p300 is negligible, second an interim region where p53 is activated due to interaction between p53 and p300, and finally the third regime where excess of p300 leads to cell stress condition. Similarly evaluation of HDAC1 on our model led to identification of the above three distinct states. Also we observe that noise in stochastic cellular system helps to reach each oscillatory state quicker than those in deterministic case. The constructed model validated different experimental findings qualitatively.

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