title: Design and analysis of a Petri net model of the Von Hippel-Lindau (VHL) tumor suppressor interaction network.
abstract: Von Hippel-Lindau (VHL) syndrome is a hereditary condition predisposing to the development of different cancer forms, related to germline inactivation of the homonymous tumor suppressor pVHL. The best characterized function of pVHL is the ubiquitination dependent degradation of Hypoxia Inducible Factor (HIF) via the proteasome. It is also involved in several cellular pathways acting as a molecular hub and interacting with more than 200 different proteins. Molecular details of pVHL plasticity remain in large part unknown. Here, we present a novel manually curated Petri Net (PN) model of the main pVHL functional pathways. The model was built using functional information derived from the literature. It includes all major pVHL functions and is able to credibly reproduce VHL syndrome at the molecular level. The reliability of the PN model also allowed in silico knockout experiments, driven by previous model analysis. Interestingly, PN analysis suggests that the variability of different VHL manifestations is correlated with the concomitant inactivation of different metabolic pathways.
authors.affiliation: Dept. of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Minervini
authors.affiliation: Dept. of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Panizzoni
authors.affiliation: Dept. of Biomedical Sciences, University of Padua, Padua, Italy; Dept. of Information Engineering, University of Padua, Padua, Italy.
authors.forename: Manuel
authors.initials: M
authors.lastname: Giollo
authors.affiliation: Dept. of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Masiero
authors.affiliation: Dept. of Information Engineering, University of Padua, Padua, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
authors.affiliation: Dept. of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Silvio C E
authors.initials: SC
authors.lastname: Tosatto
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D003198:Computer Simulation; D055786:Gene Knockout Techniques; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D060066:Protein Interaction Maps; D014158:Transcription, Genetic; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051794:Von Hippel-Lindau Tumor Suppressor Protein