Berlin 2012 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 20: Regulation
BP 20.7: Vortrag
Donnerstag, 29. März 2012, 11:30–11:45, H 1058
On the role of intrinsic noise on the response of the p53-Mdm2 module — Lidice Cruz1, Nuris Figueroa1, and •Roberto Mulet1,2 — 1Group of Complex Systems. Physics Faculty. University of Havana — 2Quantum optics and statistics Institute of Physics Albert Ludwigs University of Freiburg
The protein p53 has a well established role in protecting genomic integrity in human cells. In particular, the p53-Mdm2 feedback loop seems to be the key circuit in the response of cells to damage. Recent measurements in individual human cells have shown that p53 and its regulator Mdm2 develop sustained oscillations over long periods of time, with essentially fixed frequency but variable amplitudes. Here, we propose that the noise that stabilizes the fluctuations is the intrinsic noise due to the finite nature of the populations of p53 and Mdm2 in a single cell.
We study three stochastic models of the p53-Mdm2 circuit. The models intend to capture the response of the p53-Mdm2 circuit in its basal state, in the presence of DNA damage, and under oncogenic signals.
We show that the in all the cases the noise induced by the finite size of the populations is responsible for the existence of sustained oscillations in the response of the p53-Mdm2 circuit. This noise alone can explain most of the experimental results obtained studying the dynamics of the p53-Mdm2 circuit in individual cells.