Fourier analysis and systems identification of the p53 feedback loop.

ABSTRACT: A key circuit in the response of cells to damage is the p53-mdm2 feedback loop. This circuit shows sustained, noisy oscillations in individual human cells following DNA breaks. Here, we apply an engineering approach known as systems identification to quantify the in vivo interactions in the circuit on the basis of accurate measurements of its power spectrum. We obtained oscillation time courses of p53 and Mdm2 protein levels from several hundred cells and analyzed their Fourier spectra. We find characteristic spectra with distinct low-frequency components that are well-described by a third-order linear model with white noise. The model identifies the sign and strength of the known interactions, including a negative feedback loop between p53 and its upstream regulator. It also implies that

SUBMITTER: Geva-Zatorsky N 

PROVIDER: S-EPMC2922141 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature