Structural highlights
Function
IKBZ_HUMAN Involved in regulation of NF-kappa-B transcription factor complexes (PubMed:16513645, PubMed:16622025). Inhibits NF-kappa-B activity without affecting its nuclear translocation upon stimulation (PubMed:16513645). Inhibits DNA-binding of RELA and NFKB1/p50, and of the NF-kappa-B p65-p50 heterodimer and the NF-kappa-B p50-p50 homodimer (PubMed:16513645). Seems also to activate NF-kappa-B-mediated transcription (PubMed:16622025). In vitro, upon association with NFKB1/p50 has transcriptional activation activity and, together with NFKB1/p50 and RELA, is recruited to LCN2 promoters (PubMed:16622025). Promotes transcription of LCN2 and DEFB4 (PubMed:16622025). Is recruited to IL-6 promoters and activates IL-6 but decreases TNF-alpha production in response to LPS (By similarity). Seems to be involved in the induction of inflammatory genes activated through TLR/IL-1 receptor signaling (By similarity). Involved in the induction of T helper 17 cells (Th17) differentiation upon recognition of antigen by T cell antigen receptor (TCR) (By similarity).[UniProtKB:Q9EST8][1] [2]
Publication Abstract from PubMed
As part of the efforts to understand nuclear IkappaB function in NF-kappaB-dependent gene expression, we report an X-ray crystal structure of the IkappaBzeta ankyrin repeat domain in complex with the dimerization domain of the NF-kappaB p50 homodimer. IkappaBzeta possesses an N-terminal alpha helix that conveys domain folding stability. Affinity and specificity of the complex depend on a small portion of p50 at the nuclear localization signal. The model suggests that only one p50 subunit supports binding with IkappaBzeta, and biochemical experiments confirm that IkappaBzeta associates with DNA-bound NF-kappaB p50:RelA heterodimers. Comparisons of IkappaBzeta:p50 and p50:kappaB DNA complex crystallographic models indicate that structural rearrangement is necessary for ternary complex formation of IkappaBzeta and p50 with DNA.
Structural and biochemical analyses of the nuclear IkappaBzeta protein in complex with the NF-kappaB p50 homodimer.,Zhu N, Rogers WE, Heidary DK, Huxford T Genes Dev. 2024 Jul 19;38(11-12):528-535. doi: 10.1101/gad.351892.124. PMID:38960718[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Totzke G, Essmann F, Pohlmann S, Lindenblatt C, Jänicke RU, Schulze-Osthoff K. A novel member of the IkappaB family, human IkappaB-zeta, inhibits transactivation of p65 and its DNA binding. J Biol Chem. 2006 May 5;281(18):12645-54. PMID:16513645 doi:10.1074/jbc.M511956200
- ↑ Cowland JB, Muta T, Borregaard N. IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is controlled by IkappaB-zeta. J Immunol. 2006 May 1;176(9):5559-66. PMID:16622025 doi:10.4049/jimmunol.176.9.5559
- ↑ Zhu N, Rogers WE, Heidary DK, Huxford T. Structural and biochemical analyses of the nuclear IκBζ protein in complex with the NF-κB p50 homodimer. Genes Dev. 2024 Jul 19;38(11-12):528-535. PMID:38960718 doi:10.1101/gad.351892.124
