Data from: 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.

炎症是机体针对有害刺激与致病应激产生的复杂生理应答的组成部分。核因子κB（Nuclear Factor κB, NF-κB）家族共有五个成员，是介导炎症反应的关键调控因子，作为数百种基因的核心转录调节因子发挥功能。多种由不同刺激激活的信号通路均汇聚于NF-κB的激活过程，由此构建出一个具有高度复杂性的调控系统。越来越多的研究证实，影响信号转导通路表型结果的组分数量，可能远超经典通路表征中所纳入的组分范畴。本分析的核心目标是全面系统地呈现NF-κB信号系统的全貌。本研究收集、整理、整合并分析了来自多源的数据，包括文献资料、功能富集网络资源、蛋白质-蛋白质相互作用数据库及通路数据库，以重构出一套完整全面的、参与NF-κB激活系统并与之发生相互作用的蛋白质图谱。该重构结果表明，相较于经典通路表征，NF-κB相互作用组（interactome）的组分在数量与质量层面均存在显著差异。本分析还揭示，诸多被既往研究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关键作用。此外，该相互作用组的结构契合领结架构（bow tie architecture）的典型特征。本相互作用组将作为一个开放的网络资源，可供后续的开发、优化与分析工作使用。