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

Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy
Masahiro Yamamoto, Kiyoshi Takeda

Abstract

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

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