An Integrated Global Analysis of Compartmentalized HRAS Signaling

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Title: An Integrated Global Analysis of Compartmentalized HRAS Signaling
Authors: Santra, Tapesh
Herrero, Ana
Rodriguez, Javier
Von Kriegsheim, Alex
Iglesias-Martinez, Luis F.
Schwarz, Thomas
Higgins, Desmond G
Matallanas, David
Kolch, Walter
et al.
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Date: 12-Mar-2019
Online since: 2019-04-10T09:33:39Z
Abstract: 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.
Funding Details: European Commission - Seventh Framework Programme (FP7)
Irish Cancer Society
Science Foundation Ireland
Type of material: Journal Article
Publisher: Elsevier
Journal: Cell Reports
Volume: 26
Issue: 11
Start page: 3100
End page: 3115.e7
Copyright (published version): 2019 the Authors
Keywords: RASSubcellular compartmentalizationSignal transduction data integrationNetwork biologyProteomicsTranscriptomicsCell migrationTP53Apoptosis
DOI: 10.1016/j.celrep.2019.02.038
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Medicine Research Collection

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