An Integrated Global Analysis of Compartmentalized HRAS Signaling.
RAS
TP53
apoptosis
cell migration
network biology
proteomics
signal transduction data integration
subcellular compartmentalization
transcriptomics
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
12 03 2019
12 03 2019
Historique:
received:
16
07
2018
revised:
16
12
2018
accepted:
11
02
2019
entrez:
14
3
2019
pubmed:
14
3
2019
medline:
16
4
2020
Statut:
ppublish
Résumé
Modern omics technologies allow us to obtain global information on different types of biological networks. However, integrating these different types of analyses into a coherent framework for a comprehensive biological interpretation remains challenging. Here, we present a conceptual framework that integrates protein interaction, phosphoproteomics, and transcriptomics data. Applying this method to analyze HRAS signaling from different subcellular compartments shows that spatially defined networks contribute specific functions to HRAS signaling. Changes in HRAS protein interactions at different sites lead to different kinase activation patterns that differentially regulate gene transcription. HRAS-mediated signaling is the strongest from the cell membrane, but it regulates the largest number of genes from the endoplasmic reticulum. The integrated networks provide a topologically and functionally resolved view of HRAS signaling. They reveal distinct HRAS functions including the control of cell migration from the endoplasmic reticulum and TP53-dependent cell survival when signaling from the Golgi apparatus.
Identifiants
pubmed: 30865897
pii: S2211-1247(19)30209-8
doi: 10.1016/j.celrep.2019.02.038
pii:
doi:
Substances chimiques
Tumor Suppressor Protein p53
0
HRAS protein, human
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3100-3115.e7Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.