School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi-110067, India.
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi-110025, India.
Sci Rep. 2017 Jan 20;7:40596. doi: 10.1038/srep40596.
The stress driven dynamics of Notch-Wnt-p53 cross-talk is subjected to a few possible dynamical states governed by simple fractal rules, and allowed to decide its own fate by choosing one of these states which are contributed from long range correlation with varied fluctuations due to active molecular interaction. The topological properties of the networks corresponding to these dynamical states have hierarchical features with assortive structure. The stress signal driven by nutlin and modulated by mediator GSK3 acts as anti-apoptotic signal in this system, whereas, the stress signal driven by Axin and modulated by GSK3 behaves as anti-apoptotic for a certain range of Axin and GSK3 interaction, and beyond which the signal acts as favor-apoptotic signal. However, this stress system prefers to stay in an active dynamical state whose counterpart complex network is closest to hierarchical topology with exhibited roles of few interacting hubs. During the propagation of stress signal, the system allows the propagator pathway to inherit all possible properties of the state to the receiver pathway/pathways with slight modifications, indicating efficient information processing and democratic sharing of responsibilities in the system via cross-talk. The increase in the number of cross-talk pathways in the system favors to establish self-organization.
Notch-Wnt-p53 相互作用的应激驱动动力学受到一些可能的动态状态的控制,这些状态由简单的分形规则决定,并通过选择这些状态之一来决定自己的命运,这些状态来自于由于活性分子相互作用而产生的长程相关性和变化的波动。与这些动态状态相对应的网络的拓扑性质具有层次特征和聚类结构。由 nutlin 驱动并由介体 GSK3 调制的应激信号在该系统中充当抗凋亡信号,而由 Axin 驱动并由 GSK3 调制的应激信号在一定范围内的 Axin 和 GSK3 相互作用下表现出抗凋亡作用,超过该范围信号表现为促进凋亡信号。然而,这个应激系统倾向于保持在一个活跃的动态状态,其对应的复杂网络最接近表现出少数相互作用枢纽作用的层次拓扑结构。在应激信号的传播过程中,系统允许传播子途径将状态的所有可能特性继承给接收途径/途径,并进行轻微修改,表明系统通过相互作用进行有效的信息处理和民主分担责任。系统中相互作用途径数量的增加有利于建立自组织。