IκB-ζ: An Inducible Regulator of Nuclear Factor-κB

The innate immune system responds to various microbial substances to elicit production of cytokines, chemokines, and costimulatory molecules that regulate activation of the acquired immune system. Although the transcription factor nuclear factor (NF)¹1The abbreviations used are: ARE, AU-rich element; IL, interleukin; LPS, lipopolysaccharide; NF, nuclear factor; TAK, transforming growth factor-activated kinase; TIR, Toll/IL-1 receptor; TLR, Toll-like receptor; TNF, tumor necrosis factor; TRAF, TNF receptor-associated factor.-κB plays central roles in the induction, it remains to be clarified how appropriate genes are selectively activated with appropriate timing and duration by the multifunctional transcription factor after integration of signals activated by invasion of various pathogens. IκB-ζ is barely detectable in resting cells and is strongly induced upon stimulation of the innate immune system. The induced IκB-ζ associates with the NF-κB subunit in the nucleus and regulates its transcriptional activity both positively and negatively depending on genes. Thus, the innate immune system utilizes NF-κB as a major transcription factor and modulates its activity in a gene-specific manner by the regulatory factor IκB-ζ, which is specifically induced upon stimulation of the innate immune system. This multistep regulation of the transcription would be fundamental in selective expression of genes upon cell activation.