Hypo-phosphorylation leads to nuclear retention of NF-κB p65 due to impaired IκBα gene synthesis
Hypo-phosphorylation leads to nuclear retention of NF-κB p65 due to impaired IκBα gene synthesis
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DOI：
10.1016/j.febslet.2007.10.056
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发表时间：
2007-11-27
期刊：
影响因子：
3.5
通讯作者：
Anrather, Josef
中科院分区：
文献类型：
--
作者：
Hochrainer, Karin;Racchumi, Gianfranco;Anrather, Josef
由I κ B α引导的亚细胞定位对核因子κ B功能的调控至关重要。在这里，我们发现p65 Rel同源结构域磷酸化突变体在I kappa B α降解后被转运到细胞核中，但由于I kappa B α水平较低，它们向细胞质的重新定位被阻止。我们证明p65的残基S205、S276和S281的磷酸化不是p65和I kappa B α相互作用所必需的，而是通过积极影响基因合成来调节细胞I kappa B α水平的关键。我们的研究结果表明，磷酸化的减少导致p65的核保留，这可能是p65丝氨酸突变体转录行为改变的部分原因。(C) 2007年欧洲生化学会联合会。Elsevier B.V.版权所有。
Subcellular localization guided by I kappa B alpha is crucial for regulation of nuclear factor-kappa B function. Here, we show that p65 Rel homology domain phosphorylation mutants are transported into the nucleus after I kappa B alpha degradation, but as a consequence of lower I kappa B alpha levels their relocation to the cytosol is blocked. We demonstrate that phosphorylation of residues S205, S276, and S281 of p65 is not required for interaction between p65 and I kappa B alpha, but is pivotal for regulating cellular I kappa B alpha levels by positively affecting gene synthesis. Our findings indicate that reduction of phosphorylation leads to nuclear retention of p65, which might be partly responsible for altered transcriptional behavior of p65 serine mutants. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.