NF-κB SIGNALING COMPLEXES IN ACUTE INFLAMMATION.

Abstract

SIGNIFICANCE\nNF-κB is a master regulator of the inflammatory response and represents a key regulatory node in the complex inflammatory signaling network. Additionally, selective NF-κB transcriptional activity on specific target genes occurs through the control of redox-sensitive NF-κB interactions.\n\n\nCRITICAL ISSUES\nNF-κB is a redox-sensitive transcription factor that forms specific signaling complexes to regulate selectively the expression of target genes in acute inflammation. Protein-protein interactions with co-regulatory proteins, other transcription factors, and chromatin remodelling proteins provide transcriptional specificity to NF-κB. Furthermore, different NF-κB subunits may form distinct redox-sensitive homo and heterodimers with distinct affinities for κB sites. Recent advances: The selective NF-κB response is mediated by redox-modulated NF-κB complexes with RPS3, PIR. CBP/p300, PGC-1, AP-1, STAT3, EGR-1 and SP-1. NF-κB is cooperatively co-activated with AP-1, STAT3, EGR-1 and SP-1 during the inflammatory process, whereas NF-κB complexes with CBP/p300 and PGC-1α regulates the expression of antioxidant genes. PGC-1α may act as selective repressor of phospho-p65 towards IL-6 in acute inflammation. p65 and Nrf2 compete for binding to co-activator CBP/p300 playing opposite roles in the regulation of inflammatory genes. S-nitrosylation or tyrosine nitration favors the recruitment of specific NF-κB subunits to κB sites.\n\n\nFUTURE DIRECTIONS\nFurther research is required to elucidate the whole NF-κB interactome in order to fully characterize the complex NF-κB signalling network in redox signaling, inflammation, and cancer.