A modular model of the apoptosis machinery

Adv Exp Med Biol. 2012;736:235-45. doi: 10.1007/978-1-4419-7210-1_13.


Using a modular principle of computer hardware as a metaphor, we defined and implemented in the BioUML platform a module concept for biological pathways. BioUML provides a user interface to create modular models and convert them automatically into plain models for further simulations. Using this approach, we created the apoptosis model including 13 modules: death stimuli (TRAIL, CD95L, and TNF-α)-induced activation of caspase-8; survival stimuli (p53, EGF, and NF-κB) regulation; the mitochondria level; cytochrome C- and Smac-induced activation of caspase-3; direct activation of effector caspases by caspase-8 and - 12; PARP and apoptosis execution phase modules. Each module is based on earlier published models and extended by data from the Reactome and TRANSPATH databases. The model ability to simulate the apoptosis-related processes was checked; the modules were validated using experimental data.

Availability: http://www.biouml.org/apoptosis.shtml .

MeSH terms

  • Algorithms
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / metabolism*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Computational Biology / methods
  • Cytochromes c / metabolism
  • Epidermal Growth Factor / metabolism
  • Fas Ligand Protein / metabolism
  • HT29 Cells
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Models, Biological*
  • NF-kappa B / metabolism
  • Reproducibility of Results
  • Signal Transduction / physiology*
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • User-Computer Interface


  • Apoptosis Regulatory Proteins
  • Fas Ligand Protein
  • NF-kappa B
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • Epidermal Growth Factor
  • Cytochromes c
  • Caspases