A mathematical model of receptor-mediated apoptosis: dying to know why fasl is a trimer.
A mathematical model of receptor-mediated apoptosis: dying to know why fasl is a trimer.
复制标题
受体介导的细胞凋亡的数学模型：非常想知道为什么 fasl 是三聚体。
DOI：
10.3934/mbe.2004.1.325
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
T. Jackson
中科院分区：
文献类型：
--
作者：
R. Lai;T. Jackson
理解程序性细胞死亡的科学重要性是不可否认的；然而，由于死亡信号传播的复杂性和以前对凋亡途径的不完全了解，这一主题几乎没有被数学建模所触及。在本文中，我们使用一种机制方法来构建目前对受体介导的细胞凋亡的理解，其直接目标是分离受体三聚化在这一过程中所起的作用。分析和模拟表明，如果死亡信号要在低受体、高配体浓度下成功传递，Fas三聚化不太可能成为信号传播的驱动力。然而，在高受体和低配体浓度下，数学模型说明了FasL聚集三个Fas受体的能力如何对传播凋亡信号的下游事件至关重要。
The scientific importance of understanding programmed cell death is undeniable; however, the complexity of death signal propagation and the formerly incomplete knowledge of apoptotic pathways has left this topic virtually untouched by mathematical modeling. In this paper, we use a mechanistic approach to frame the current understanding of receptor-mediated apoptosis with an immediate goal of isolating the role receptor trimerization plays in this process. Analysis and simulation suggest that if the death signal is to be successful at low-receptor, high-ligand concentration, Fas trimerization is unlikely to be the driving force in the signal propagation. However at high-receptor and low-ligand concentrations, the mathematical model illustrates how the ability of FasL to cluster three Fas receptors can be crucially important for downstream events that propagate the apoptotic signal.