A statistical mechanics investigation of Unfolded Protein Response across organisms

Abstract

Living systems rely on coordinated molecular interactions, especially those related to gene expression and protein activity. The Unfolded Protein Response is a crucial mechanism in eukaryotic cells, activated when unfolded proteins exceed a critical threshold. It maintains cell homeostasis by enhancing protein folding, initiating quality control, and activating degradation pathways when damage is irreversible. This response functions as a dynamic signaling network, with proteins as nodes and their interactions as edges. We analyze these protein-protein networks across different organisms to understand their intricate intra-cellular interactions and behaviors. In this work, analyzing twelve organisms, we assess how fundamental measures in network theory can individuate seed-proteins and specific pathways across organisms. We employ network robustness to evaluate and compare the strength of the investigated PPI networks, and the structural controllability of complex networks to find and compare the sets of driver nodes necessary to control the overall networks. We find that network measures are related to phylogenetics, and advanced network methods can identify main pathways of significance in the complete Unfolded Protein Response mechanism.

References in corpus (10)

• Network robustness and fragility: Percolation on random graphs
• Resilience of the Internet to random breakdowns
• Attack vulnerability of complex networks
• Breakdown of the Internet under intentional attack
• Betweenness Centrality in Large Complex Networks
• Control Principles of Complex Networks
• Robustness and resilience of complex networks
• Exact Controllability of Complex Networks
• Controllability analysis of the directed human protein interaction network identifies disease genes and drug targets
• Structural Controllability to Unveil Hidden Regulation Mechanisms in Unfolded Protein Response: the Role of Network Models