Nguyen Lan K, Matallanas David G, Romano David, Kholodenko Boris N, Kolch Walter
a Systems Biology Ireland ; University College Dublin ; Belfield , Dublin , Ireland.
Cell Cycle. 2015;14(2):189-99. doi: 10.4161/15384101.2014.973743.
How do biochemical signaling pathways generate biological specificity? This question is fundamental to modern biology, and its enigma has been accentuated by the discovery that most proteins in signaling networks serve multifunctional roles. An answer to this question may lie in analyzing network properties rather than individual traits of proteins in order to elucidate design principles of biochemical networks that enable biological decision-making. We discuss how this is achieved in the MST2/Hippo-Raf-1 signaling network with the help of mathematical modeling and model-based analysis, which showed that competing protein interactions with affinities controlled by dynamic protein modifications can function as Boolean computing devices that determine cell fate decisions. In addition, we discuss areas of interest for future research and highlight how systems approaches would be of benefit.
生物化学信号通路是如何产生生物学特异性的？这个问题是现代生物学的基础，而信号网络中大多数蛋白质具有多种功能这一发现，更是凸显了其神秘性。这个问题的答案可能在于分析网络特性而非蛋白质的个体特征，以便阐明能够实现生物学决策的生物化学网络的设计原则。我们将借助数学建模和基于模型的分析，讨论在MST2/河马-Raf-1信号网络中是如何做到这一点的，研究表明，由动态蛋白质修饰控制亲和力的竞争性蛋白质相互作用，可以充当决定细胞命运决策的布尔计算装置。此外，我们还将讨论未来研究的关注领域，并强调系统方法将如何发挥作用。
