Picking a Signaling Pathway

Abstract

How is specificity gained when numerous genes are regulated by a single transcription factor in response to diverse stimuli? Hoffman et al. (see the Perspective by Ting and Endy) examined how a transcription factor called nuclear factor-κB (NF-κB) is differentially controlled by three different isoforms of an inhibitor protein called IκB. They combined computational modeling with biochemical data that they obtained from genetically engineered cells that express only one IκB isoform. During the cell's exposure to a stimulus, a bimodal and temporal signal processing mechanism determines which IκB-NF-κB pathway and downstream target genes get activated. A. Hoffmann, A. Levchenko, M. L. Scott, D. Baltimore, The IκB-NF-κB signaling module: Temporal control and selective gene activation. Science 298, 1241-1245 (2002). [Abstract] [Full Text] A. Y. Ting, D. Endy, Decoding NF-κB signaling. Science 298, 1189-1190 (2002). [Summary] [Full Text]