title: Mathematical modeling and sensitivity analysis of the integrated TNFα-mediated apoptotic pathway for identifying key regulators.
abstract: TNFα-mediated apoptosis is one of the complex and tightly regulated cellular processes as it involves the activation of both pro- and anti-apoptotic signaling pathways. Thus, it is important to elucidate the molecular players of this process and their dynamics in order to gain an in-depth understanding of the mechanisms underlying apoptosis. To this end, we proposed an integrated model of TNFα-mediated apoptosis pathway in Type I cells, formulated based on the principles of mass action kinetics. The model includes major apoptotic modules-the extrinsic and intrinsic pathways, the NFκB survival signaling and various regulatory mechanisms. We performed simulations and sensitivity analyses to study the role of NFκB pathway in regulating apoptosis, and identified IAP as one of the more potent regulators of apoptosis.
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, Centros, Singapore 138668, Singapore. geoffrey_koh@bti.a-star.edu.sg
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Koh
authors.forename: Dong-Yup
authors.initials: DY
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D003198:Computer Simulation; D055785:Gene Knockdown Techniques; D008954:Models, Biological; D016328:NF-kappa B; D015398:Signal Transduction / Q000502:physiology*; D049490:Systems Biology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3