Ubiquitin Signaling to NF-κB

Nuclear factor-κB (NF-κB) proteins are a family of transcription factors that control the expression of genes in key cellular processes. As aberrant activation of NF-κB is linked to the pathogenesis of human diseases, it must be tightly regulated to ensure that an appropriate physiological outcome is achieved. One such regulatory mechanism, termed ubiquitination, involves the modification of preexisting proteins with ubiquitin, rapidly altering their fate. Ubiquitination events are intricately entwined in NF-κB signaling pathways, owing to the range of ubiquitin linkages available and the reversible nature of the modification. Here we present an overview of some of the best-characterized NF-κB signaling pathways, highlighting their regulation by ubiquitin-mediated events. We emphasize the role of ubiquitin ligases, deubiquitinases, and ubiquitin-binding molecules in regulating this crucial family of transcription factors, NF-κB.