RelA control of IκBα phosphorylation -: A positive feedback loop for high affinity NF-κB complexes
RelA control of IκBα phosphorylation -: A positive feedback loop for high affinity NF-κB complexes
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DOI：
10.1074/jbc.m212216200
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发表时间：
2003-08-15
影响因子：
4.8
通讯作者：
Qwarnstrom, EE
中科院分区：
文献类型：
--
作者：
Yang, L;Ross, K;Qwarnstrom, EE
核因子-kappaB-IkappaB复合体的形成调节着核因子-kappaB活性的水平和特异性。定量分析表明，RelA-NF-kappaB诱导的IkappaBalpha结合是通过抑制物滞留和磷酸化来调节的。RERA导致IkappaBalpha的磷酸化和降解增加，并随着抑制剂浓度的增加而单调增强。体内分析表明，RELA诱导的IkappaBalpha/relA相互作用是特异的、可饱和的和依赖于磷酸化的。此外，研究还表明，在细胞因子诱导的通路激活过程中，磷酸化同时调节着复合体的水平和亲和力，并表现出平均亲和力的增加与复合体水平的降低相一致。结果表明，IkappaB-IkappaBalpha复合体形成的RelA调节依赖于IkappaBalpha的磷酸化，IkappaBalpha/NF-kappaB的结合是动态的，并由亚基的浓度决定。此外，他们认为，通过磷酸化调节复杂水平和亲和力，影响系统稳定状态，参与选择性激活核因子-kappaB途径。
NF-kappaB-IkappaB complex formation regulates the level and specificity of NF-kappaB activity. Quantitative analyses showed that RelA-NF-kappaB-induced IkappaBalpha binding is regulated through inhibitor retention and phosphorylation. RelA caused an increase in IkappaBalpha phosphorylation and in degradation, which was enhanced monotonically with inhibitor concentration. In vivo analysis demonstrated the RelA-induced IkappaBalpha/RelA interactions to be specific, saturable, and phosphorylation-dependent. In addition, it showed that phosphorylation regulates both the level and affinity of the complexes and demonstrated an increased average affinity to coincide with reduction in the level of complexes during cytokine-induced pathway activation. The data show that RelA regulation of NF-kappaB-IkappaBalpha complex formation is IkappaBalpha phosphorylation-dependent and that IkappaBalpha/NF-kappaB binding is dynamic and determined by concentration of the subunits. In addition, they suggest that regulation of both complex levels and affinities through phosphorylation, with effects on the system steady state, participate in selective activation of the NF-kappaB pathway.