A hallmark of the NF-B transcription response to inflammatory cytokines is the remarkably rapid rate of robust activation and subsequent signal repression. Although the rapidity of postinduction repression is explained partly by the fact that the gene for I B␣ is strongly induced by NF-B, the newly synthesized I B␣ still must enter the nucleus and compete for binding to NF-B with the very large number of B sites in the DNA. We present results from real-time binding kinetic experiments, demonstrating that I B␣ increases the dissociation rate of NF-B from the DNA in a highly efficient kinetic process. Analysis of various I B mutant proteins shows that this process requires the C-terminal PEST sequence and the weakly folded fifth and sixth ankyrin repeats of I B␣. Mutational stabilization of these repeats reduces the efficiency with which I B␣ enhances the dissociation rate.binding kinetics ͉ disordered proteins ͉ protein-DNA interaction ͉ transcription ͉ surface plasmon resonance

BackgroundWaves propagating in "excitable media" is a reliable way to transmit signals in space. A fascinating example where living cells comprise such a medium is Dictyostelium D. which propagates waves of chemoattractant to attract distant cells. While neutrophils chemotax in a similar fashion as Dictyostelium D., it is unclear if chemoattractant waves exist in mammalian tissues and what mechanisms could propagate them.ResultsWe propose that chemoattractant cytokine waves may naturally develop as a result of NF-κB response. Using a heuristic mathematical model of NF-κB-like circuits coupled in space we show that the known characteristics of NF-κB response favor cytokine waves.ConclusionsWhile the propagating wave of cytokines is generally beneficial for inflammation resolution, our model predicts that there exist special conditions that can cause chronic inflammation and re-occurrence of acute inflammatory response.

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