Lessons from mathematically modeling the NF-κB pathway

Abstract

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.