Role of nuclear IκB proteins in the regulation of host immune responses

A variety of microbial components activate a transcription factor called nuclear factor-κB (NF-κB) that plays an essential role in the optimal activation of host immune systems. The transcriptional activity of NF-κB is tightly regulated at multiple steps in immune signaling pathways, because excessive activation is detrimental to the host. One mechanism to prevent NF-κB activation is mediated by cytoplasmic IκB family proteins. Although cytoplasmic IκBs interact with NF-κB subunits in the cytoplasm of unstimulated cells, IκBs are rapidly degraded on stimulation, allowing free NF-κB to translocate into the nucleus and activate the transcription of genes encoding various immune mediators. After the translocation of NF-κB from the cytoplasm to the nucleus, nuclear proteins that are structurally similar to cytoplasmic IκBs take part in the regulation of NF-κB transcriptional activity, as activators or inhibitors, by associating with NF-κB subunits. Therefore, the regulatory IκB-like nuclear molecules are described as “nuclear IκB proteins.” In this review, the in vivo function of the nuclear IκB proteins, Bcl-3, IκBζ, and IκBNS in the context of host immune responses and diseases will be discussed.