Alternative splicing in the NF-κB signaling pathway

Activation of transcription factor NF-κB can affect the expression of several hundred genes, many of which are involved in inflammation and immunity. The proper NF-κB transcriptional response is primarily regulated by post-translational modification of NF-κB signaling constituents. Herein, we review...

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Bibliographic Details
Published in:Gene 2008-11, Vol.423 (2), p.97-107
Main Authors: Leeman, Joshua R., Gilmore, Thomas D.
Format: Article
Language:English
Subjects:
mRNA
NF-kappaB
Signal transduction
Splicing
Toll-like receptors
Tumor necrosis factor receptor
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Summary:Activation of transcription factor NF-κB can affect the expression of several hundred genes, many of which are involved in inflammation and immunity. The proper NF-κB transcriptional response is primarily regulated by post-translational modification of NF-κB signaling constituents. Herein, we review the accumulating evidence suggesting that alternative splicing of NF-κB signaling components is another means of controlling NF-κB signaling. Several alternative splicing events in both the tumor necrosis factor and Toll/interleukin-1 NF-κB signaling pathways can inhibit the NF-κB response, whereas others enhance NF-κB signaling. Alternative splicing of mRNAs encoding some NF-κB signaling components can be induced by prolonged exposure to an NF-κB-activating signal, such as lipopolysaccharide, suggesting a mechanism for negative feedback to dampen excessive NF-κB signaling. Moreover, some NF-κB alternative splicing events appear to be specific for certain diseases, and could serve as therapeutic targets or biomarkers.
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2008.07.015