title: The dynamics of stress p53-Mdm2 network regulated by p300 and HDAC1.
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 [Formula: see text] 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.
authors: Bioinformatics Division, Institute of Cytology and Preventive Oncology, Noida, India.
authors: Akshit
authors: A
authors: Arora
authors: Saurav
authors: S
authors: Gera
authors: Tanuj
authors: T
authors: Maheshwari
authors: Dhwani
authors: D
authors: Raghav
authors: Md Jahoor
authors: MJ
authors: Alam
authors: R K Brojen
authors: RK
authors: Singh
authors: Subhash M
authors: SM
authors: Agarwal
mesh_terms: D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D055550:Protein Stability; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D015398:Signal Transduction; D013269:Stochastic Processes; D013312:Stress, Physiological; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1