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Reconstruction and analysis of a large-scale binary Ras-effector signaling network.
Simona Catozzi1,2, Camille Ternet1,2, Alize Gourrege1,2
1Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Cell Communication and Signaling : CCS
|March 5, 2022
Summary
This study maps the Ras-effector network, revealing extensive crosstalk and novel functions. The comprehensive interactome serves as a foundation for understanding Ras signaling in various cellular contexts and diseases like cancer.
Area of Science:
- Cellular signaling and molecular networks
- Systems biology and bioinformatics
Background:
- Ras is a central regulator of cell fate, controlling multiple downstream pathways.
- While some Ras effector pathways are well-studied, many remain poorly understood.
Purpose of the Study:
- To construct a comprehensive and unbiased Ras-effector network.
- To analyze signaling crosstalk, feedbacks, localization, and functions within the network.
Main Methods:
- Reconstruction of a Ras-effector network using public pathway and protein-protein interaction (PPI) databases.
- Analysis of 43 effector proteins and 12 effector classes, resulting in a 3-layer signaling network.
- Generation of class-specific subnetworks and functional enrichment analysis.
Main Results:
- The network comprises 2290 proteins and 19,080 PPIs, with interactions increasing in downstream layers.
- Significant crosstalk was identified among the 12 effector classes.
- Functional enrichment revealed known and novel functions for specific effector pathways.
Conclusions:
- The developed Ras-effector network is a reference interactome for defining network boundaries.
- It can be contextualized for specific cell types or cancer patient data.
- The network provides a basis for studying systems properties like crosstalk and pathway redundancy.
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