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. 2012;7(3):e32678.
doi: 10.1371/journal.pone.0032678. Epub 2012 Mar 5.

Charting the NF-κB pathway interactome map

Paolo Tieri  1 , Alberto Termanini, Elena Bellavista, Stefano Salvioli, Miriam Capri, Claudio Franceschi
Affiliations

Charting the NF-κB pathway interactome map

Paolo Tieri et al. PLoS One. 2012.

Abstract

Inflammation is part of a complex physiological response to harmful stimuli and pathogenic stress. The five components of the Nuclear Factor κB (NF-κB) family are prominent mediators of inflammation, acting as key transcriptional regulators of hundreds of genes. Several signaling pathways activated by diverse stimuli converge on NF-κB activation, resulting in a regulatory system characterized by high complexity. It is increasingly recognized that the number of components that impinges upon phenotypic outcomes of signal transduction pathways may be higher than those taken into consideration from canonical pathway representations. Scope of the present analysis is to provide a wider, systemic picture of the NF-κB signaling system. Data from different sources such as literature, functional enrichment web resources, protein-protein interaction and pathway databases have been gathered, curated, integrated and analyzed in order to reconstruct a single, comprehensive picture of the proteins that interact with, and participate to the NF-κB activation system. Such a reconstruction shows that the NF-κB interactome is substantially different in quantity and quality of components with respect to canonical representations. The analysis highlights that several neglected but topologically central proteins may play a role in the activation of NF-κB mediated responses. Moreover the interactome structure fits with the characteristics of a bow tie architecture. This interactome is intended as an open network resource available for further development, refinement and analysis.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The three interactomes DI (a), UI (b) and MCI (c) and the resulting UNION interactome (d) as from Cytoscape layout, available in the Dataset S1 as .cys file.
Datasets and interactomes have been reconstructed following procedures described in materials and methods section. Nodes represent proteins and links are evidence-based physical interactions. Node size and color are proportional to betweenness centrality values (red: high, green: low; not comparable among different interactomes). Isolated proteins show no evidence of physical interactions with any other proteins within the same dataset.
Figure 2
Figure 2. Datasets DI, U and MC share a relatively low number of proteins, as reported by the figures in the intersections.
Datasets are quite differentiated in their composition and share only the 2.6% of the whole UNION set (16 out of 622).
Figure 3
Figure 3. The UNION interactome is composed by 622 proteins, including the five NF-κB subunits.
NF-κB is able to regulate the expression of 426 proteins (DG set, see main text). A subset (384 proteins, present in the APID database, out of 426) has been checked for PPIs (see Dataset S1). Forty nine proteins are shared by both the UNION and the DG sets, establishing a feedback loop: “interaction with NF-κB pathway → transcription factor activation → transcriptional regulation → interaction with NF-κB pathway”, meaning that 13% of the identified NF-κB-regulated genes express proteins that play a direct role in the UNION interactome.
See this image and copyright information in PMC

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