A comprehensive modular map of molecular interactions in RB/E2F pathway

Mol Syst Biol. 2008:4:173. doi: 10.1038/msb.2008.7. Epub 2008 Mar 4.


We present, here, a detailed and curated map of molecular interactions taking place in the regulation of the cell cycle by the retinoblastoma protein (RB/RB1). Deregulations and/or mutations in this pathway are observed in most human cancers. The map was created using Systems Biology Graphical Notation language with the help of CellDesigner 3.5 software and converted into BioPAX 2.0 pathway description format. In the current state the map contains 78 proteins, 176 genes, 99 protein complexes, 208 distinct chemical species and 165 chemical reactions. Overall, the map recapitulates biological facts from approximately 350 publications annotated in the diagram. The network contains more details about RB/E2F interaction network than existing large-scale pathway databases. Structural analysis of the interaction network revealed a modular organization of the network, which was used to elaborate a more summarized, higher-level representation of RB/E2F network. The simplification of complex networks opens the road for creating realistic computational models of this regulatory pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Physiological Phenomena
  • Computational Biology / methods
  • Computer Simulation
  • E2F Transcription Factors / metabolism*
  • Gene Expression Regulation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Models, Biological
  • Mutation
  • Protein Interaction Mapping
  • Retinoblastoma Protein / metabolism*
  • Software
  • Systems Biology
  • Urinary Bladder Neoplasms / metabolism


  • E2F Transcription Factors
  • Retinoblastoma Protein