Cargando…

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

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 Fac...

Descripción completa

Detalles Bibliográficos
Autores principales: Minervini, Giovanni, Panizzoni, Elisabetta, Giollo, Manuel, Masiero, Alessandro, Ferrari, Carlo, Tosatto, Silvio C. E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041725/
https://www.ncbi.nlm.nih.gov/pubmed/24886840
http://dx.doi.org/10.1371/journal.pone.0096986
_version_ 1782318707451625472
author Minervini, Giovanni
Panizzoni, Elisabetta
Giollo, Manuel
Masiero, Alessandro
Ferrari, Carlo
Tosatto, Silvio C. E.
author_facet Minervini, Giovanni
Panizzoni, Elisabetta
Giollo, Manuel
Masiero, Alessandro
Ferrari, Carlo
Tosatto, Silvio C. E.
author_sort Minervini, Giovanni
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4041725
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-40417252014-06-09 Design and Analysis of a Petri Net Model of the Von Hippel-Lindau (VHL) Tumor Suppressor Interaction Network Minervini, Giovanni Panizzoni, Elisabetta Giollo, Manuel Masiero, Alessandro Ferrari, Carlo Tosatto, Silvio C. E. PLoS One Research Article 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. Public Library of Science 2014-06-02 /pmc/articles/PMC4041725/ /pubmed/24886840 http://dx.doi.org/10.1371/journal.pone.0096986 Text en © 2014 Minervini et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Minervini, Giovanni
Panizzoni, Elisabetta
Giollo, Manuel
Masiero, Alessandro
Ferrari, Carlo
Tosatto, Silvio C. E.
Design and Analysis of a Petri Net Model of the Von Hippel-Lindau (VHL) Tumor Suppressor Interaction Network
title Design and Analysis of a Petri Net Model of the Von Hippel-Lindau (VHL) Tumor Suppressor Interaction Network
title_full Design and Analysis of a Petri Net Model of the Von Hippel-Lindau (VHL) Tumor Suppressor Interaction Network
title_fullStr Design and Analysis of a Petri Net Model of the Von Hippel-Lindau (VHL) Tumor Suppressor Interaction Network
title_full_unstemmed Design and Analysis of a Petri Net Model of the Von Hippel-Lindau (VHL) Tumor Suppressor Interaction Network
title_short Design and Analysis of a Petri Net Model of the Von Hippel-Lindau (VHL) Tumor Suppressor Interaction Network
title_sort design and analysis of a petri net model of the von hippel-lindau (vhl) tumor suppressor interaction network
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041725/
https://www.ncbi.nlm.nih.gov/pubmed/24886840
http://dx.doi.org/10.1371/journal.pone.0096986
work_keys_str_mv AT minervinigiovanni designandanalysisofapetrinetmodelofthevonhippellindauvhltumorsuppressorinteractionnetwork
AT panizzonielisabetta designandanalysisofapetrinetmodelofthevonhippellindauvhltumorsuppressorinteractionnetwork
AT giollomanuel designandanalysisofapetrinetmodelofthevonhippellindauvhltumorsuppressorinteractionnetwork
AT masieroalessandro designandanalysisofapetrinetmodelofthevonhippellindauvhltumorsuppressorinteractionnetwork
AT ferraricarlo designandanalysisofapetrinetmodelofthevonhippellindauvhltumorsuppressorinteractionnetwork
AT tosattosilvioce designandanalysisofapetrinetmodelofthevonhippellindauvhltumorsuppressorinteractionnetwork