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

التفاصيل البيبلوغرافية
العنوان: Boolean network-based model of the Bcl-2 family mediated MOMP regulation
المؤلفون: Jozef Ulicny, Tomas Tokar, Zdenko Turcan
المصدر: Theoretical Biology & Medical Modelling
بيانات النشر: BioMed Central, 2013.
سنة النشر: 2013
مصطلحات موضوعية: Systems biology, Molecular Networks (q-bio.MN), Boolean network, Information Storage and Retrieval, Health Informatics, Apoptosis, Biology, 03 medical and health sciences, 0302 clinical medicine, Bcl-2 family, Modelling and Simulation, Quantitative Biology - Molecular Networks, 030304 developmental biology, 0303 health sciences, Mitochondrial outer membrane permeabilization, Mitochondrial outer membrane permeabilisation, Effector, Research, Cell biology, Antiapoptotic protein, Proto-Oncogene Proteins c-bcl-2, 030220 oncology & carcinogenesis, Modeling and Simulation, FOS: Biological sciences, Mitochondrial Membranes
الوصف: Background 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. Methods 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. Results 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. Conclusions 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.
اللغة: English
تدمد: 1742-4682
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e26b87c737a08438f9b1a59808a37bfTest
http://europepmc.org/articles/PMC3716804Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....9e26b87c737a08438f9b1a59808a37bf
قاعدة البيانات: OpenAIRE