NFKBIZ gene

The NFKBIZ gene belongs to the "ankyrin repeat family" and is induced by lipopolysaccharide (LPS). The C-terminal part of the encoded protein, which contains the ankyrin repeats, has a high sequence similarity with the I kappa B protein family. The latter are known to play a role in inflammatory responses to LPS through their interaction with NF-B proteins via ankyrin repeat domains. Studies in mice indicate that this gene product is one of the nuclear I kappa B proteins and an activator of interleukin-6 production.

The encoded protein is involved in the regulation of NF-kappa-B transcription factor complexes (Cowland JB et al. 2006). Inhibits the activity of NF-kappa-B without affecting its nuclear translocation upon stimulation (Totzke G et al. 2006).

Also appears to activate NF-kappa-B-mediated transcription. In vitro, it has transcriptional activation activity after association with NFKB1/p50 and is recruited to LCN2 promoters together with NFKB1/p50 and RELA (Cowland JB et al. 2006). Promotes transcription of LCN2 and DEFB4 (Cowland JB et al. 2006). Recruited to interleukin-6 promotersand activates IL-6, but decreases TNF-alpha production in response to LPS. Appears to be involved in the induction of inflammatory genes activated by TLR/IL-1 receptor signaling. Is involved in the induction of differentiation of T helper 17 cells (Th17) after recognition of the antigen by the T cell antigen receptor (TCR). Is important for TLR-mediated induction of proinflammatory cytokines (Petnicki-Ocwieja T et al. (2023).

Diseases associated with NFKBIZ include psoriasis and Premature Ovarian Failure 18 (POF18).

1. Chen S et al. (1997) Molecular basis of the catalytic differences among DT-diaphorase of human, rat, and mouse. J Biol Chem 272:1437-1439.
2. Cowland JB et al. (2006) IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is controlled by IkappaB-zeta. J Immunol 176:5559-5566.

3. Petnicki-Ocwieja T et al. (2023) Borrelia burgdorferi initiates early transcriptional re-programming in macrophages that supports long-term suppression of inflammation. PLoS Pathog 19:e1011886.

4. Totzke G et al. (2006) A novel member of the IkappaB family, human IkappaB-zeta, inhibits transactivation of p65 and its DNA binding. J Biol Chem 281:12645-12654.