NFKBIZ

Description

The NFKBIZ (NFKB inhibitor zeta) is a protein-coding gene located on chromosome 3.

NFKBIZ is a gene that encodes a protein called NF-kappa-B inhibitor zeta (IκBζ). This protein belongs to the ankyrin-repeat family and is induced by lipopolysaccharide (LPS). The C-terminal portion of IκBζ, which contains the ankyrin repeats, is very similar to the I kappa B family of proteins. These proteins play a role in inflammatory responses to LPS by interacting with NF-κB proteins through ankyrin-repeat domains. Studies in mice show that IκBζ is a nuclear I kappa B protein and an activator of IL-6 production. There are two different forms of IκBζ produced from the NFKBIZ gene. NFKBIZ has been linked to cancer, specifically diffuse large B-cell lymphoma (DLBCL). The part of the genome containing NFKBIZ is frequently amplified in the activated B-cell (ABC) subgroup of DLBCL. Recent studies have found mutations in the 3-prime untranslated region of NFKBIZ that increase the amount of IκBζ made in ABC DLBCL. IκBζ is necessary for the production of the CCL2 (MCP1) cytokine, which attracts macrophages to remove cancer cells. The flavonoid apigenin has been shown to reduce the expression of the NFKBIZ gene.

NFKBIZ is involved in regulating NF-kappa-B transcription factor complexes. It inhibits NF-kappa-B activity without affecting its nuclear translocation. It inhibits DNA-binding of RELA and NFKB1/p50, as well as the NF-kappa-B p65-p50 heterodimer and the NF-kappa-B p50-p50 homodimer. However, NFKBIZ also seems to activate NF-kappa-B-mediated transcription. When associated with NFKB1/p50, it has transcriptional activation activity and is recruited to LCN2 promoters along with NFKB1/p50 and RELA. It promotes transcription of LCN2 and DEFB4. NFKBIZ is recruited to IL-6 promoters, activates IL-6, but decreases TNF-alpha production in response to LPS. It is believed to be involved in the induction of inflammatory genes activated through TLR/IL-1 receptor signaling and in the induction of T helper 17 cell (Th17) differentiation upon recognition of antigen by the T cell antigen receptor (TCR).

NFKBIZ is also known as I-kappa-B-zeta, IKBZ, INAP, IkappaB-zeta, MAIL, ikB-zeta, ikappaBzeta.

Associated Diseases

WES Whole Exome Sequencing