Role of nuclear IkappaB proteins in the regulation of host immune responses.
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 responses and diseases will be discussed.
Yamamoto
Masahiro
M
Department of Microbiology and Immunology, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Takeda
Kiyoshi
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology; D045643:DNA Repair Enzymes; D006801:Humans; D020672:I-kappa B Proteins / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology; D011506:Proteins / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D045643:DNA Repair Enzymes; D020672:I-kappa B Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins; C454819:Nfkbid protein, mouse; C476254:N4BP2 protein, human; C417234:NFKBIZ protein, human; C485947:Nfkbiz protein, mouse