JCB logo
Get More Out of Microscopy - Agilent iMIC 2000
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 13 September 2004. doi:10.1083/jcb.200404158
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 166, Number 6, 839-851
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bentele, M.
Right arrow Articles by Eils, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bentele, M.
Right arrow Articles by Eils, R.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

 Mathematical modeling reveals threshold mechanism in CD95-induced apoptosis

M. Bentele1, I. Lavrik2, M. Ulrich1, S. Stößer2, D.W. Heermann3, H. Kalthoff4, P.H. Krammer2, and R. Eils1

1 Division Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
2 Immunogenetics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
3 Institute for Theoretical Physics, University of Heidelberg, 69120 Heidelberg, Germany
4 Molecular Oncology, Clinic for General Surgery and Thoracic Surgery, University of Kiel, 24098 Kiel, Germany

Address correspondence to R. Eils, DKFZ, Division Theoretical Bioinformatics, Im Neuenheimer Feld 580, Heidelberg 69120, Germany. Tel.: (49) 6221-423600; Fax: (49) 6221-423610; email: r.eils{at}dkfz.de

Mathematical modeling is required for understanding the complex behavior of large signal transduction networks. Previous attempts to model signal transduction pathways were often limited to small systems or based on qualitative data only. Here, we developed a mathematical modeling framework for understanding the complex signaling behavior of CD95(APO-1/Fas)-mediated apoptosis. Defects in the regulation of apoptosis result in serious diseases such as cancer, autoimmunity, and neurodegeneration. During the last decade many of the molecular mechanisms of apoptosis signaling have been examined and elucidated. A systemic understanding of apoptosis is, however, still missing. To address the complexity of apoptotic signaling we subdivided this system into subsystems of different information qualities. A new approach for sensitivity analysis within the mathematical model was key for the identification of critical system parameters and two essential system properties: modularity and robustness. Our model describes the regulation of apoptosis on a systems level and resolves the important question of a threshold mechanism for the regulation of apoptosis.

Key Words: mathematical modeling; CD95-induced apoptosis; sensitivity analysis; parameter estimation; threshold mechanism

M. Bentele and I. Lavrik contributed equally to this work.

Abbreviations used in this paper: CHX, cyclohexamide; DD, death domain; DISC, death-inducing signaling complex.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

A model of cell death
Nicole LeBrasseur
J. Cell Biol. 2004 166: 760-761. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents