Mathematical modeling and sensitivity analysis of the integrated TNFα-mediated apoptotic pathway for identifying key regulators

  • Authors:

  • Geoffrey Koh;Dong-Yup Lee

  • Affiliations:

  • Bioprocessing Technology Institute, Agency for Science, Technology and Research (ASTAR), 20 Biopolis Way, #06-01, Centros, Singapore 138668, Singapore;Bioprocessing Technology Institute, Agency for Science, Technology and Research (ASTAR), 20 Biopolis Way, #06-01, Centros, Singapore 138668, Singapore and Department of Chemical and Biomolecular E ...

  • Venue:
  • Computers in Biology and Medicine
  • Year:
  • 2011

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Abstract

TNF@a-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 TNF@a-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 NF@kB survival signaling and various regulatory mechanisms. We performed simulations and sensitivity analyses to study the role of NF@kB pathway in regulating apoptosis, and identified IAP as one of the more potent regulators of apoptosis.