A Mathematical Model of Receptor-Mediated Apoptosis: Dying to Know Why FasL is a Trimer

The scientific importance of understanding programmed cell death isundeniable; however, the complexity of death signal propagation andthe formerly incomplete knowledge of apoptotic pathways has left thistopic virtually untouched by mathematical modeling. In this paper, weuse a mechanistic approach...

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Bibliographic Details
Main Authors: Ronald Lai, Trachette L. Jackson
Format: Article
Language:English
Published: AIMS Press 2004-06-01
Series:Mathematical Biosciences and Engineering
Subjects:
Online Access:https://www.aimspress.com/article/doi/10.3934/mbe.2004.1.325
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Summary:The scientific importance of understanding programmed cell death isundeniable; however, the complexity of death signal propagation andthe formerly incomplete knowledge of apoptotic pathways has left thistopic virtually untouched by mathematical modeling. In this paper, weuse a mechanistic approach to frame the current understanding ofreceptor-mediated apoptosis with an immediate goal of isolating therole receptor trimerization plays in this process. Analysis andsimulation suggest that if the death signal is to be successful at low-receptor, high-ligand concentration, Fas trimerization is unlikely tobe the driving force in the signal propagation. However at high-receptor and low-ligand concentrations, the mathematical modelillustrates how the ability of FasL to cluster three Fas receptors canbe crucially important for downstream events that propagate theapoptotic signal.
ISSN:1551-0018