Analysis of a minimal model for p53 oscillations

Oscillatory behaviours in genetic networks are important examples for studying the principles underlying the dynamics of cellular regulation. Recently the team of Alon has reported a surprisingly rich oscillatory response of the p53 tumor suppressor to irradiation stress et al. [Lahav, G., Rosenfeld, N., Sigal, A., Geva-Zatorsky, N., Levine, AJ., Elowitz, M.B., Alon, U., 2004. Dynamics of the p53Mdm2 feedback loop in individual cells. Nat. Genet. 36 (2), 147-150; Geva-Zatorsky, N., Rosenfeld, N., Itzkovitz, S., Milo, R., Sigal, A., Dekel, E., Yarnitzky, T., Liron, Y., Polak, P., Lahav, G., Alon, U., 2006. Oscillations and variability in the p53 system. Mol. Syst. Biol. 2, 2006.0033]. Several models for this system have been proposed by different groups, based essentially on negative feedback loops. In this paper we investigate in detail oscillations and stability in a deterministic time delayed differential model of the core circuit for p53 expression. This model is representative of a class of modelling approaches of this system, based on a "minimal" set of well-established biomolecular regulations. Depending on the protein degradation rates we show the existence of bifurcations between a stable steady state and oscillations both in presence and absence of stress. (C) 2007 Elsevier Ltd. All rights reserved.