It takes two to regulate

Two isoforms of the IκB inhibitor of NF-κB are required to turn oscillation into steady regulation during chronic stimulation, according to Kearns et al. (page 659). The use of two out-of-phase regulators may be a common means to control signaling pathways.

NF-κB activation triggers expression of IκBα, which leads to down-regulation of the signaling pathway and a decrease in IκBα transcription. However, under chronic stimulation the NF-κB signaling pathway becomes reactivated as soon as the amount of IκBα drops below a certain level. Thus, in cells engineered so that IκBα is the only IκB isoform present, NF-κB activity oscillates over many cycles. In unmodified cells, however, NF-κB activity is steady, and computational modeling suggested the existence of an active damping mechanism that limits fluctuation.

Kearns et al. found that IκBε expression was also induced...