NF-kappa-B inhibitor zeta (IκBζ) is a protein that in humans is encoded by the NFKBIZgene.[5][6][7] This gene is a member of the ankyrin-repeat family and is induced by lipopolysaccharide (LPS). The C-terminal portion of the encoded product which contains the ankyrin repeats, shares high sequence similarity with the I kappa B family of proteins. The latter are known to play a role in inflammatory responses to LPS by their interaction with NF-κB proteins through ankyrin-repeat domains. Studies in mouse indicate that this gene product is one of the nuclear I kappa B proteins and an activator of IL-6 production. Two transcript variants encoding different isoforms have been found for this gene.[8]
NFKBIZ has been implicated as an oncogene in diffuse large B-cell lymphoma (DLBCL). Specifically, genomic locus containing this gene is recurrently amplified in copy number in the activated B-cell (ABC) subgroup of DLBCL.[9] More recently, a recurrence of somatic mutations affecting the 3-prime untranslated region of NFKBIZ were found to promote NFKBIZ expression in ABC DLBCL.[10]
IκBζ is required for expression of the SASPCCL2 (MCP1) cytokine, which recruits macrophages to remove cancer cells.[7]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Eto A, Muta T, Yamazaki S, Takeshige K (February 2003). "Essential roles for NF-kappa B and a Toll/IL-1 receptor domain-specific signal(s) in the induction of I kappa B-zeta". Biochemical and Biophysical Research Communications. 301 (2): 495–501. doi:10.1016/S0006-291X(02)03082-6. PMID12565889.
Kitamura H, Kanehira K, Okita K, Morimatsu M, Saito M (November 2000). "MAIL, a novel nuclear I kappa B protein that potentiates LPS-induced IL-6 production". FEBS Letters. 485 (1): 53–6. doi:10.1016/S0014-5793(00)02185-2. PMID11086164. S2CID85416608.
Shiina T, Morimatsu M, Kitamura H, Ito T, Kidou S, Matsubara K, Matsuda Y, Saito M, Syuto B (October 2001). "Genomic organization, chromosomal localization, and promoter analysis of the mouse Mail gene". Immunogenetics. 53 (8): 649–55. doi:10.1007/s00251-001-0376-x. PMID11797098. S2CID12387932.
Ito T, Morimatsu M, Oonuma T, Shiina T, Kitamura H, Syuto B (November 2004). "Transcriptional regulation of the MAIL gene in LPS-stimulated RAW264 mouse macrophages". Gene. 342 (1): 137–43. doi:10.1016/j.gene.2004.07.032. PMID15527973.
Yamamoto M, Yamazaki S, Uematsu S, Sato S, Hemmi H, Hoshino K, Kaisho T, Kuwata H, Takeuchi O, Takeshige K, Saitoh T, Yamaoka S, Yamamoto N, Yamamoto S, Muta T, Takeda K, Akira S (July 2004). "Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta". Nature. 430 (6996): 218–22. Bibcode:2004Natur.430..218Y. doi:10.1038/nature02738. PMID15241416. S2CID4384768.
Yamaji D, Kitamura H, Kimura K, Matsushita Y, Okada H, Shiina T, Morimatsu M, Saito M (April 2004). "Cloning of bovine MAIL and its mRNA expression in white blood cells of Holstein cows". Veterinary Immunology and Immunopathology. 98 (3–4): 175–84. doi:10.1016/j.vetimm.2003.12.004. PMID15010226.
