Alternative splicing in the NF-κB signaling pathway

Activation of transcription factor NF-kappa B can affect the expression of several hundred genes, many of which are involved in inflammation and immunity. The proper NF-kappa B transcriptional response is primarily regulated by post-translational modification of NF-kappa B signaling constituents. Herein, we review the accumulating evidence suggesting that alternative splicing of NF-kappa B signaling components is another means of controlling NF-kappa B signaling. Several alternative splicing events in both the tumor necrosis factor and Toll/interleukin-1 NF-kappa B signaling pathways can inhibit the NF-kappa B response, whereas others enhance NF-kappa B signaling. Alternative splicing of mRNAs encoding some NF-kappa B signaling components can be induced by prolonged exposure to an NF-kappa B-activating signal, such as lipopolysaccharide, suggesting a mechanism for negative feedback to dampen excessive NF-kappa B signaling. Moreover, some NF-kappa B alternative splicing events appear to be specific for certain diseases, and could serve as therapeutic targets or biomarkers. (c) 2008 Elsevier B.V. All rights reserved.