کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2187462 1096120 2008 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Nuclear IκB Protein IκBζ Specifically Binds NF-κB p50 Homodimers and Forms a Ternary Complex on κB DNA
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
The Nuclear IκB Protein IκBζ Specifically Binds NF-κB p50 Homodimers and Forms a Ternary Complex on κB DNA
چکیده انگلیسی

Although they share sequence homology to classical cytoplasmic IκB inhibitors of transcription factor NF-κB, the proteins IκBζ, Bcl-3, and IκBNS function in the nucleus as factors that influence NF-κB-dependent gene expression profiles. Through the use of purified recombinant proteins and by comparison with the classical IκB protein IκBα, we have discovered mechanistic details of the interaction between IκBζ and functional NF-κB dimers. Whereas IκBα and other classical IκB proteins bind tightly to NF-κB dimers that possess the p65 subunit, IκBζ binds preferentially to NF-κB p50 homodimers. This altered specificity is particularly interesting in light of the fact that both NF-κB subunits exhibit high sequence and structural homology, while the IκBα and IκBζ proteins are also conserved in primary amino acid sequence. We further show that IκBζ is capable of forming a stable ternary complex with the NF-κB p50 homodimer and κB DNA. Again, this is a stark contrast from IκBα, which inhibits NF-κB p65 homodimer binding to NF-κB target DNA sequences. Removal of the DNA sequences flanking the NF-κB binding site does not directly affect the interaction of p50 and IκBζ. Rather, we have discovered that the carboxy-terminal glycine-rich region of the NF-κB p50 homodimer is involved in mediating high-affinity binding of IκBζ and NF-κB p50. We conclude that the NF-κB p50 homodimer functions as a legitimate activator of gene expression through formation of a ternary complex between itself, IκBζ, and DNA. The requirement for formation of this complex could explain why the nuclear IκB protein IκBζ is absolutely required for expression of the pluripotent pro-inflammatory cytokine interleukin-6 in peritoneal macrophages.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 379, Issue 1, 23 May 2008, Pages 122–135
نویسندگان
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