Charting the NF-κB Pathway Interactome Map

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.炎症是机体应对有害刺激与致病应激的复杂生理应答的组成部分。核因子κB（Nuclear Factor κB，NF-κB）家族的五个成员是炎症反应的关键介导因子，可作为数百个基因的核心转录调控因子。多种由不同刺激激活的信号通路汇聚于NF-κB的激活过程，由此形成一个高度复杂的调控系统。越来越多的研究表明，影响信号转导通路表型结果的组分数量，可能多于经典通路表征中所纳入的组分数量。本分析的核心目标是构建NF-κB信号系统更为全面的系统性图景。研究人员从文献、功能富集网络资源、蛋白质相互作用及通路数据库等多种数据源中收集、整理、整合并分析相关数据，以重构出与NF-κB激活系统相互作用并参与该系统的蛋白质的统一全景图谱。该重构结果显示，相较于经典通路表征，NF-κB相互作用组在组分的数量与质量层面均存在显著差异。本分析揭示，诸多被忽视但在拓扑结构上处于核心位置的蛋白质，可能在NF-κB介导的应答激活过程中发挥重要作用。此外，该相互作用组的结构符合领结（bow tie）架构的特征。本相互作用组将作为开放的网络资源，可供后续开发、优化与分析使用。