Signaling via the <scp>NFκB</scp> system

<jats:p>The nuclear factor kappa B (<jats:styled-content style="fixed-case">NFκB</jats:styled-content>) family of transcription factors is a key regulator of immune development, immune responses, inflammation, and cancer. The <jats:styled-content style="fixed-case">NFκB</jats:styled-content> signaling system (defined by the interactions between <jats:styled-content style="fixed-case">NFκB</jats:styled-content> dimers, <jats:styled-content style="fixed-case">IκB</jats:styled-content> regulators, and <jats:styled-content style="fixed-case">IKK</jats:styled-content> complexes) is responsive to a number of stimuli, and upon ligand–receptor engagement, distinct cellular outcomes, appropriate to the specific signal received, are set into motion. After almost three decades of study, many signaling mechanisms are well understood, rendering them amenable to mathematical modeling, which can reveal deeper insights about the regulatory design principles. While other reviews have focused on upstream, receptor proximal signaling (Hayden MS, Ghosh S. Signaling to NF‐κB. <jats:italic>Genes Dev</jats:italic> 2004, 18:2195–2224; Verstrepen L, Bekaert T, Chau TL, Tavernier J, Chariot A, Beyaert R. TLR‐4, IL‐1R and TNF‐R signaling to NF‐κB: variations on a common theme. <jats:italic>Cell Mol Life Sci</jats:italic> 2008, 65:2964–2978), and advances through computational modeling (Basak S, Behar M, Hoffmann A. Lessons from mathematically modeling the NF‐κB pathway. <jats:italic>Immunol Rev</jats:italic> 2012, 246:221–238; Williams R, Timmis J, Qwarnstrom E. Computational models of the NF‐KB signalling pathway. <jats:italic>Computation</jats:italic> 2014, 2:131), in this review we aim to summarize the current understanding of the <jats:styled-content style="fixed-case">NFκB</jats:styled-content> signaling system itself, the molecular mechanisms, and systems properties that are key to its diverse biological functions, and we discuss remaining questions in the field. <jats:italic>WIREs Syst Biol Med</jats:italic> 2016, 8:227–241. doi: 10.1002/wsbm.1331</jats:p><jats:p>This article is categorized under: <jats:list list-type="explicit-label"> <jats:list-item><jats:p>Biological Mechanisms > Cell Signaling</jats:p></jats:list-item> <jats:list-item><jats:p>Models of Systems Properties and Processes > Mechanistic Models</jats:p></jats:list-item> <jats:list-item><jats:p>Physiology > Organismal Responses to Environment</jats:p></jats:list-item> </jats:list></jats:p>