Lessons from mathematically modeling the NF-κB pathway.

Mathematical modeling has proved to be a critically important approach in the study of many complex networks and dynamic systems in physics, engineering, chemistry, and biology. The nuclear factor κB (NF-κB) system consists of more than 50 proteins and protein complexes and is both a highly networked and dynamic system. To date, mathematical modeling has only addressed a small fraction of the molecular species and their regulation, but when employed in conjunction with experimental analysis has already led to important insights. Here, we provide a personal account of studying how the NF-κB signaling system functions using mathematical descriptions of the molecular mechanisms. We focus on the insights gained about some of the key regulatory components: the control of the steady state, the signaling dynamics, and signaling crosstalk. We also discuss the biological relevance of these regulatory systems properties.