Regulation of NF-κB by TNF family cytokines

The NF-kappa B family of inducible transcription factors is activated in response to a variety of stimuli. Amongst the best-characterized inducers of NF-kappa B are members of the TNF family of cytokines. Research on NF-kappa B and TNF have been tightly intertwined for more than 25 years. Perhaps the most compelling examples of the interconnectedness of NF-kappa B and the TNF have come from analysis of knock-out mice that are unable to activate NF-kappa B. Such mice die embryonically, however, deletion of TNF or TNFR1 can rescue the lethality thereby illustrating the important role of NF-kappa B as the key regulator of transcriptional responses to TNF. The physiological connections between NF-kappa B and TNF cytokines are numerous and best explored in articles focusing on a single TNF family member. Instead, in this review, we explore general mechanisms of TNF cytokine signaling, with a focus on the upstream signaling events leading to activation of the so-called canonical and noncanonical NF-kappa B pathways by TNFR1 and CD40, respectively. (C) 2014 Elsevier Ltd. All rights reserved.