Boolean network-based model of the Bcl-2 family mediated MOMP regulation.

Tomas Tokar, Zdenko Turcan, Jozef Ulicny

Theoretical biology & medical modelling 2013 Jun 14

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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.

Citation

Tomas Tokar, Zdenko Turcan, Jozef Ulicny. Boolean network-based model of the Bcl-2 family mediated MOMP regulation. Theoretical biology & medical modelling. 2013 Jun 14;10:40