Mathematical modeling identified c-FLIP as an apoptotic switch in death receptor induced apoptosis.
Apoptosis is an essential process to get rid of injured or unwanted cells. In this study, we proposed a mathematical modeling for death receptor mediated apoptosis to investigate the role of c-FLIP in controlling the balance between apoptosis and survival. In order to get insight into how NF-kappa B mediated pro-survival pathway affects the outcome of our modeling, we implemented reduced models without taking such regulation into consideration. Our simulation revealed that c-FLIP could act as a pivotal death or life switch and this switch-like behavior is bistable, irreversible, and robust. We introduce a new term, probability apoptosis, to delineate the likelihood in occurrence of apoptosis events. This simulation system is plausible and may offer several valuable clinical indications for the abnormal apoptosis related disease, such as cancer.
Han
Lihui
L
Department of Immunology, School of Medicine, Shandong University, Jinan 250012 China. hanlihui@sdu.edu.cn
Zhao
Yishu
Y
Jia
Xiaoqing
X
D000818:Animals; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002470:Cell Survival; D004789:Enzyme Activation; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism*; D015398:Signal Transduction
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D016328:NF-kappa B; D053218:Receptors, Death Domain; D053148:Caspase 3; D053181:Caspase 8