The enhancement of stability of p53 in MTBP induced p53-MDM2 regulatory network.
We have modeled an MTBP-MDM2-p53 regulatory network by integrating p53-MDM2 autoregulatory model (Proctor and Gray, 2008) with the effect of a cellular protein MTBP (MDM2 binding protein) which is allowed to bind with MDM2 (Brady et al., 2005). We study this model to investigate the activation of p53 and MDM2 steady state levels induced by MTBP protein under different stress conditions. Our simulation results in three approaches namely deterministic, Chemical Langevin equation and stochastic simulation of Master equation show a clear transition from damped limit cycle oscillation to fixed point oscillation during a certain time period with constant stress condition in the cell. This transition is the signature of transition of p53 and MDM2 levels from activated state to stabilized steady state levels. We present various phase diagrams to show the transition between unstable and stable states of p53 and MDM2 concentration levels and also their possible relations among critical value of the parameters at which the respective protein level reach stable steady states. In the stochastic approach, the dynamics of the proteins become noise induced process depending on the system size. We found that this noise enhances the stability of the p53 steady state level.
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.
Md Jahoor
MJ
Alam
Nishat
N
Fatima
Gurumayum Reenaroy
GR
Devi
Ravins
R K Brojen
RK
Singh
D002352:Carrier Proteins / Q000378:metabolism*; D003198:Computer Simulation; D053263:Gene Regulatory Networks; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002352:Carrier Proteins; C485931:MTBP protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2