Alternative splicing in the NF-kappaB signaling pathway.
Activation of transcription factor NF-kappaB can affect the expression of several hundred genes, many of which are involved in inflammation and immunity. The proper NF-kappaB transcriptional response is primarily regulated by post-translational modification of NF-kappaB signaling constituents. Herein, we review the accumulating evidence suggesting that alternative splicing of NF-kappaB signaling components is another means of controlling NF-kappaB signaling. Several alternative splicing events in both the tumor necrosis factor and Toll/interleukin-1 NF-kappaB signaling pathways can inhibit the NF-kappaB response, whereas others enhance NF-kappaB signaling. Alternative splicing of mRNAs encoding some NF-kappaB signaling components can be induced by prolonged exposure to an NF-kappaB-activating signal, such as lipopolysaccharide, suggesting a mechanism for negative feedback to dampen excessive NF-kappaB signaling. Moreover, some NF-kappaB alternative splicing events appear to be specific for certain diseases, and could serve as therapeutic targets or biomarkers.
Leeman
Joshua R
JR
Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
Gilmore
Thomas D
TD
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase