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Investigation of the signaling events that lead to the activation of the transcription factor nuclear factor κB (NF-κB) has been a hotbed for the discovery of previously uncharacterized signaling mechanisms. The important role that nondegradative polyubiquitin chains play in these processes is now well recognized; however, precisely how they orchestrate NF-κB signaling is still a matter of much controversy. A recent study has challenged the dogmatic view by demonstrating that interleukin-1β (IL-1β), a major proinflammatory cytokine, activates two consecutive pathways, the “RING” and “zinc” pathways, to coordinate early and late activation of NF-κB, respectively. This study introduces a paradigm shift in the still-evolving mechanism of regulation of NF-κB.