The NF-?B multidimer system model: a knowledge base to explore diverse biological contexts

The nuclear factor ?B (NF-?B) system is critical for various biological functions in numerous cell types, including the inflammatory response, cell proliferation, survival, differentiation, and pathogenic responses. Each cell type is characterized by a subset of 15 NF-?B dimers whose activity is regulated in a stimulus-responsive manner. Numerous studies have produced different mathematical models that account for cell type–specific NF-?B activities. However, whereas the concentrations or abundances of NF-?B subunits may differ between cell types, the biochemical interactions that constitute the NF-?B signaling system do not. Here, we synthesized a consensus mathematical model of the NF-?B multidimer system, which could account for the cell type–specific repertoires of NF-?B dimers and their cell type–specific activation and cross-talk. Our review demonstrates that these distinct cell type–specific properties of NF-?B signaling can be explained largely as emergent effects of the cell type–specific expression of NF-?B monomers. The consensus systems model represents a knowledge base that may be used to gain insights into the control and function of NF-?B in diverse physiological and pathological scenarios and that describes a path for generating similar regulatory knowledge bases for other pleiotropic signaling systems.