Pd Palladium

Activation of death receptors (TNFR and Fas) can trigger either survival or cell death according to the cell type and the cellular conditions. In other words, the same signal can have antagonist responses. On one hand, the cell can survive by activating the NFκB signalling pathway. On the other hand, it can die by apoptosis or necrosis. Apoptosis is a suicide mechanism, i.e., an orchestrated way to disrupt cellular components and pack them into specialized vesicles that can be easily removed from the environment, whereas necrosis is a type of death that involves release of intracellular components in the surrounding tissues, possibly causing inflammatory response and severe injury. We, biologists and theoreticians, have recapitulated and integrated known biological data from the literature into an influence diagram describing the molecular events leading to each possible outcome. The diagram has been translated into a dynamical Boolean model. Simulations of wild type, mutant cells and drug treatments qualitatively match current data, and predict several novel mutant phenotypes, along with general characteristics of the cell fate decision mechanism: transient activation of some key proteins in necrosis, mutual inhibitory cross-talks between the three pathways. Our model can further be used to assess contradictory data and address specific biological questions through in silico experiments.