Design and Analysis of a Petri Net Model of the Von Hippel-Lindau (VHL) Tumor Suppressor Interaction Network

• DOI: 10.1371/journal.pone.0096986
• Publication Date: 2014-06-02T21:15:03Z
• Authors: Giovanni Minervini; Elisabetta Panizzoni; Manuel Giollo; Alessandro Masiero; Carlo Ferrari; Silvio C. E. Tosatto
• Keywords: 0303 health sciences; Transcription, Genetic; Science; Q; R; Hypoxia-Inducible Factor 1, alpha Subunit; Models, Biological; 3. Good health; Gene Knockout Techniques; 03 medical and health sciences; Von Hippel-Lindau Tumor Suppressor Protein; Medicine; Cluster Analysis; Humans; Computer Simulation; Protein Interaction Maps; Algorithms; Research Article

Von Hippel-Lindau (VHL) syndrome is a hereditary condition predisposing to the development of different cancer forms, related germline inactivation homonymous tumor suppressor pVHL. The best characterized function pVHL ubiquitination dependent degradation Hypoxia Inducible Factor (HIF) via proteasome. It also involved in several cellular pathways acting as molecular hub and interacting with more than 200 proteins. Molecular details plasticity remain large part unknown. Here, we present novel manually curated Petri Net (PN) model main functional pathways. was built using information derived from literature. includes all major functions able credibly reproduce VHL at level. reliability PN allowed silico knockout experiments, driven by previous analysis. Interestingly, analysis suggests that variability manifestations correlated concomitant metabolic