Gene network dynamics controlling keratinocyte migration

【原创】DNA转录成RNA，RNA翻译成蛋白质，蛋白质磷酸化，激活，泛素化，蛋白质定位。。。

在生物受到刺激后，这些生物过程是在什么时间范围内完成的？

这篇文章给出了生物分子发生作用的时间尺度，对于构建基因调控网络有指导意义。

Cellular responses can be the result of either a single stimulus or a time-sequential activation of different signaling pathways upon an initial trigger signal (Janes et al, 2006). In the latter case, the response is most likely distributed over hours and requires the involvement of both protein signaling and gene regulation in a feedback-entangled process. Elucidating such a complex decision making is inherently difficult. It is hard to define and experimentally observe all required functional cellular components at a sufficiently high sampling rate. Furthermore, only a few detailed in silico models integrating both signaling and gene regulation have been developed so far (Yeang et al, 2005; Ernst et al, 2007).

Assuming that long-term cellular behavior is reflected in the gene expression kinetics.Here, we propose a different complexity reduction approach based on the timescale separation of cellular events. Such events are encoded in the temporal modulation of molecule concentrations, that is, in changes of mRNA concentrations, protein complex formation, translocation in space, conformational changes or their molecular modifications. They occur on different timescales ranging from milliseconds to seconds (e.g. induced conformational changes) via seconds and minutes (e.g. post-translational protein modification) up to hours and days for gene expression kinetics and/or even years by epigenetic regulation.

In this study, we consider a cellular decision that is reached on a timescale of hours. Thus, it is the protein turnover rate in the range of hours that is the slowest evolving variable. Furthermore, we assume the proportionality between protein and mRNA concentrations such that both evolve on the same timescale. Enhancement of the basal biochemical protein activities by post translational events occurs on a much shorter timescale in the order of minutes, for example, shifting the balances between a phosphorylated and nonphosphorylated form, formation and temporal presence of a multimeric protein complex or temporal translocation to its location of activity. Hence, adiabatically approximating these fast protein modulations and describing proteins in terms of their mRNA concentrations leads to the formulation of a gene regulatory network model, whose dynamics should provide information similar to a comprehensive protein interaction network (cf. Supplementary information for a detailed mathematical treatment). As a practical consequence, information on the former network can be easily accessed experimentally by time-resolved DNA microarray measurements.

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