Robustness analysis identifies the plausible model of the Bcl-2 apoptotic switch
Robustness analysis identifies the plausible model of the Bcl-2 apoptotic switch
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DOI：
10.1016/j.febslet.2007.09.063
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发表时间：
2007-10-30
期刊：
影响因子：
3.5
通讯作者：
Shen, Pingping
中科院分区：
文献类型：
--
作者：
Chen, Chun;Cui, Jun;Shen, Pingping
本文通过数学建模和稳健性分析，对比了两种相互竞争的B细胞淋巴瘤2(Bcl2)细胞凋亡开关模型。由于试图解释全有或全无决定细胞凋亡的模型需要类似开关的行为，因此超敏感性被用作比较的标准。我们的结果成功地表明，直接激活模型在细胞条件下更可靠地实现了稳健的开关。此外，通过研究Bcl2凋亡开关的其他重要特征(包括低Bax基础激活、抗凋亡蛋白的抑制作用和对微小扰动的不敏感性)的稳健性，进一步支持了直接激活模型。总而言之，我们认为直接激活模型是对Bcl-2凋亡开关更合理的解释。(C)2007年欧洲生化学会联合会。爱思唯尔出版，版权所有。
In this paper two competing models of the B-cell lymphoma 2 (Bcl-2) apoptotic switch were contrasted by mathematical modeling and robustness analysis. Since switch-like behaviors are required for models that attempt to explain the all-or-none decisions of apoptosis, ultrasensitivity was employed as a criterion for comparison. Our results successfully exhibit that the direct activation model operates more reliably to achieve a robust switch in cellular conditions. Moreover, by investigating the robustness of other important features of the Bcl-2 apoptotic switch (including low Bax basal activation, inhibitory role of anti-apoptotic proteins and insensitivity to small perturbations) the direct activation model was further supported. In all, we identified the direct activation model as a more plausible explanation for the Bcl-2 apoptotic switch. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.