The Ubiquitination of NF-κB Subunits in the Control of Transcription

Nuclear factor (NF)-kappa B has evolved as a latent, inducible family of transcription factors fundamental in the control of the inflammatory response. The transcription of hundreds of genes involved in inflammation and immune homeostasis require NF-kappa B, necessitating the need for its strict control. The inducible ubiquitination and proteasomal degradation of the cytoplasmic inhibitor of kappa B (I kappa B) proteins promotes the nuclear translocation and transcriptional activity of NF-kappa B. More recently, an additional role for ubiquitination in the regulation of NF-kappa B activity has been identified. In this case, the ubiquitination and degradation of the NF-kappa B subunits themselves plays a critical role in the termination of NF-kappa B activity and the associated transcriptional response. While there is still much to discover, a number of NF-kappa B ubiquitin ligases and deubiquitinases have now been identified which coordinate to regulate the NF-kappa B transcriptional response. This review will focus the regulation of NF-kappa B subunits by ubiquitination, the key regulatory components and their impact on NF-kappa B directed transcription.