Tokar Tomas, Turcan Zdenko, Ulicny Jozef
Department of Biophysics, University of PJ Safarik, Jesenna 5, 04001 Kosice, Slovakia.
Theor Biol Med Model. 2013 Jun 14;10:40. doi: 10.1186/1742-4682-10-40.
Mitochondrial outer membrane permeabilization (MOMP) is one of the most important points in the majority of apoptotic signaling cascades and it is controlled by a network of interactions between the members of the Bcl-2 family.
To understand the role of individual members of this family within the MOMP regulation, we have constructed a Boolean network-based model of interactions between the Bcl-2 proteins.
Computational simulations have revealed the existence of trapping states which, independently from the incoming stimuli, block the occurrence of MOMP. Our results emphasize the role of the antiapoptotic protein Mcl-1 in the majority of these configurations. We demonstrate here the importance of the Bid and Bim for activation of effectors Bax and Bak, and the irreversibility of this activation. The model further points to the antiapoptotic protein Bcl-w as a key factor preventing Bax activation.
In spite of relative simplicity, the Boolean network-based model provides useful insight into main functioning logic of the Bcl-2 switch, consistent with experimental findings.
线粒体外膜通透性改变（MOMP）是大多数凋亡信号级联反应中最重要的环节之一，它受Bcl-2家族成员间相互作用网络的控制。
为了解该家族单个成员在MOMP调控中的作用，我们构建了一个基于布尔网络的Bcl-2蛋白相互作用模型。
计算模拟揭示了存在捕获状态，该状态独立于传入刺激，可阻止MOMP的发生。我们的结果强调了抗凋亡蛋白Mcl-1在大多数这些构型中的作用。我们在此证明了Bid和Bim对效应器Bax和Bak激活的重要性，以及这种激活的不可逆性。该模型进一步指出抗凋亡蛋白Bcl-w是阻止Bax激活的关键因素。
尽管相对简单，但基于布尔网络的模型为Bcl-2开关的主要功能逻辑提供了有用的见解，与实验结果一致。
