Autonomous Oscillations of NF-κB

The nuclear factor κB (NF-κB) signaling pathway plays a crucial role in regulating immune responses, inflammation, and cell survival. After the discovery of NF-κB by Ranjan Sen and David Baltimore as a nuclear factor that binds near the κ light-chain gene in activated B-cells [1], extensive research has been conducted to uncover key biochemical mechanisms underlying the pathway and the downstream genes regulated by NF-κB. The core regulatory module of NF-κB/IκB (inhibitor of NF-κB)/IKK (IκB kinase) has also been a leading example of cell signaling pathways that can produce oscillatory activities, particularly in response to the pro-inflammatory cytokine tumor necrosis factor α (TNF-α). Despite this status, the existence and function of NF-κB oscillations was a contentious topic in the early years. In this chapter, we touch on the history, progression, and outlook of the quest to decipher the properties and biological function of NF-κB oscillations.