NFKBIZ

NF-kappa-B inhibitor zeta (IκBζ) is a protein that in humans is encoded by the NFKBIZ gene.[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-B 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
Identifiers
AliasesNFKBIZ, IKBZ, INAP, MAIL, NFKB inhibitor zeta
External IDsOMIM: 608004 MGI: 1931595 HomoloGene: 12734 GeneCards: NFKBIZ
Orthologs
SpeciesHumanMouse
Entrez

64332

80859

Ensembl

ENSG00000144802

ENSMUSG00000035356

UniProt

Q9BYH8

Q9EST8

RefSeq (mRNA)

NM_031419
NM_001005474

NM_001159394
NM_001159395
NM_030612

RefSeq (protein)

NP_001005474
NP_113607

NP_001152866
NP_001152867
NP_085115

Location (UCSC)Chr 3: 101.83 – 101.86 MbChr 16: 55.63 – 55.66 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Clinical relevance

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 SASP CCL2 (MCP1) cytokine, which recruits macrophages to remove cancer cells.[7]

The flavonoid apigenin has been shown to reduce gene expression of IκBζ.[11]

References

  1. GRCh38: Ensembl release 89: ENSG00000144802 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000035356 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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. PMID 12565889.
  6. Totzke G, Essmann F, Pohlmann S, Lindenblatt C, Jänicke RU, Schulze-Osthoff K (May 2006). "A novel member of the IkappaB family, human IkappaB-zeta, inhibits transactivation of p65 and its DNA binding". The Journal of Biological Chemistry. 281 (18): 12645–54. doi:10.1074/jbc.M511956200. PMID 16513645.
  7. Alexander E, Hildebrand DG, Schulze-Osthoff K, Essmann F (2013). "IκBζ is a regulator of the senescence-associated secretory phenotype in DNA damage- and oncogene-induced senescence". Journal of Cell Science. 126 (Pt 16): 3738–3745. doi:10.1242/jcs.128835. PMID 23781024.
  8. "Entrez Gene: NFKBIZ nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta".
  9. Nogai H, Wenzel SS, Hailfinger S, Grau M, Kaergel E, Seitz V, et al. (September 2013). "IκB-ζ controls the constitutive NF-κB target gene network and survival of ABC DLBCL". Blood. 122 (13): 2242–50. doi:10.1182/blood-2013-06-508028. PMID 23869088. S2CID 18427175.
  10. Arthur SE, Jiang A, Grande BM, Alcaide M, Cojocaru R, Rushton CK, et al. (October 2018). "Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma". Nature Communications. 9 (1): 4001. Bibcode:2018NatCo...9.4001A. doi:10.1038/s41467-018-06354-3. PMC 6167379. PMID 30275490.
  11. Lim H, Heo MY, Kim HP (2019). "Flavonoids: Broad Spectrum Agents on Chronic Inflammation". Biomolecules & Therapeutics. 27 (3): 241–253. doi:10.4062/biomolther.2019.034. PMC 6513185. PMID 31006180.

Further reading

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