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

The nuclear factor 0B (NF-0B) 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-0B dimers whose activity is regulated in a stimulus-responsive manner. Numerous studies have produced different mathematical models that account for cell type-specific NF-0B ac-tivities. However, whereas the concentrations or abundances of NF-0B subunits may differ between cell types, the biochemical interactions that constitute the NF-0B signaling system do not. Here, we synthesized a consen-sus mathematical model of the NF-0B multidimer system, which could account for the cell type-specific reper-toires of NF-0B dimers and their cell type-specific activation and cross-talk. Our review demonstrates that these distinct cell type-specific properties of NF-0B signaling can be explained largely as emergent effects of the cell type-specific expression of NF-0B monomers. The consensus systems model represents a knowledge base that may be used to gain insights into the control and function of NF-0B in diverse physiological and pathological scenarios and that describes a path for generating similar regulatory knowledge bases for other pleiotropic sig-naling systems.

Automated summary

The NF-0B system plays critical roles in various biological functions in different cell types. A consensus mathematical model of the NF-0B multidimer system has been created to explain the cell type-specific activation and cross-talk of NF-0B dimers. It is shown that the cell type-specific properties of NF-0B signaling can be largely explained by the cell type-specific expression of NF-0B monomers. This model provides a knowledge base for understanding and studying NF-0B in different physiological and pathological scenarios, and can be used as a path for generating similar regulatory knowledge bases for other pleiotropic signaling systems.