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• W2010187658 abstract "Although they share sequence homology to classical cytoplasmic I kappaB inhibitors of transcription factor NF-kappaB, the proteins I kappaB zeta, Bcl-3, and I kappa BNS function in the nucleus as factors that influence NF-kappaB-dependent gene expression profiles. Through the use of purified recombinant proteins and by comparison with the classical I kappaB protein I kappaB alpha, we have discovered mechanistic details of the interaction between I kappaB zeta and functional NF-kappaB dimers. Whereas I kappaB alpha and other classical I kappaB proteins bind tightly to NF-kappaB dimers that possess the p65 subunit, I kappaB zeta binds preferentially to NF-kappaB p50 homodimers. This altered specificity is particularly interesting in light of the fact that both NF-kappaB subunits exhibit high sequence and structural homology, while the I kappaB alpha and I kappaB zeta proteins are also conserved in primary amino acid sequence. We further show that I kappaB zeta is capable of forming a stable ternary complex with the NF-kappaB p50 homodimer and kappaB DNA. Again, this is a stark contrast from I kappaB alpha, which inhibits NF-kappaB p65 homodimer binding to NF-kappaB target DNA sequences. Removal of the DNA sequences flanking the NF-kappaB binding site does not directly affect the interaction of p50 and I kappaB zeta. Rather, we have discovered that the carboxy-terminal glycine-rich region of the NF-kappaB p50 homodimer is involved in mediating high-affinity binding of I kappaB zeta and NF-kappaB p50. We conclude that the NF-kappaB p50 homodimer functions as a legitimate activator of gene expression through formation of a ternary complex between itself, I kappaB zeta, and DNA. The requirement for formation of this complex could explain why the nuclear I kappaB protein I kappaB zeta is absolutely required for expression of the pluripotent pro-inflammatory cytokine interleukin-6 in peritoneal macrophages." @default.
• W2010187658 created "2016-06-24" @default.
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• W2010187658 date "2008-05-01" @default.
• W2010187658 modified "2023-09-30" @default.
• W2010187658 title "The Nuclear IκB Protein IκBζ Specifically Binds NF-κB p50 Homodimers and Forms a Ternary Complex on κB DNA" @default.
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• W2010187658 doi "https://doi.org/10.1016/j.jmb.2008.03.060" @default.
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