Bottani Samuel, Grammaticos Basile
Laboratoire Matières et Systèmes Complexes, Université Paris 7, CNRS UMR 7057, c.c. 7056, 75205 Paris Cedex 13, France.
J Theor Biol. 2007 Nov 21;249(2):235-45. doi: 10.1016/j.jtbi.2007.04.026. Epub 2007 Jul 26.
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, A.J., Elowitz, M.B., Alon, U., 2004. Dynamics of the p53-Mdm2 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.
基因网络中的振荡行为是研究细胞调控动力学潜在原理的重要示例。最近，阿隆团队报道了p53肿瘤抑制因子对辐射应激等的惊人丰富的振荡反应[拉哈夫，G.，罗森菲尔德，N.，西加尔，A.，格瓦 - 扎托尔斯基，N.，莱文，A.J.，埃洛维茨，M.B.，阿隆，U.，2004年。单个细胞中p53 - Mdm2反馈回路的动力学。《自然遗传学》36(2)，147 - 150；格瓦 - 扎托尔斯基，N.，罗森菲尔德，N.，伊茨科维茨，S.，米洛，R.，西加尔，A.，德凯尔，E.，亚尔尼茨基，T.，利龙，Y.，波拉克，P.，拉哈夫，G.，阿隆，U.，2006年。p53系统中的振荡和变异性。《分子系统生物学》2，2006.0033]。不同研究小组基于负反馈回路提出了该系统的几种模型。在本文中，我们详细研究了p53表达核心回路的确定性时滞微分模型中的振荡和稳定性。该模型代表了基于一组成熟的“最小”生物分子调控的此类系统建模方法。根据蛋白质降解率，我们展示了在有应激和无应激情况下稳定稳态与振荡之间的分岔存在情况。
