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...
Autores principales: | , , , , , |
---|---|
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 |