NF-κB p52, RelB and c-Rel are transported into the nucleus via a subset of importin α molecules
NF-κB p52, RelB and c-Rel are transported into the nucleus via a subset of importin α molecules
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DOI：
10.1016/j.cellsig.2008.03.012
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发表时间：
2008-08-01
影响因子：
4.8
通讯作者：
Julkunen, Ilkka
中科院分区：
文献类型：
--
作者：
Fagerlund, Riku;Melen, Krister;Julkunen, Ilkka
在静息细胞中，NF-κ B转录因子作为潜在的非活性复合物保留在细胞质中，直到它们被激活并迅速转运到细胞核中。我们表明，所有NF-κ B蛋白进口到细胞核通过一个子集的输入素亚型。我们的数据表明，经典和替代途径的NF-κ B组分对输入a分子的特异性略有不同。基于体外翻译的和仙台病毒感染诱导的或TNF-α刺激的内源性NF-κ B蛋白的结合实验的结果，可以预测NF-κ B B蛋白对输入素α分子的特异性是不同的，并且随着输入的二聚体的组成而变化。p52蛋白直接与输入蛋白α 3、α 4、α 5和α 6结合，c-Rel通过先前描述的单组分核定位信号（NLS）与输入蛋白α 5、α 6和α 7结合。在这里，我们表明，RelB，而不是，有一个二分精氨酸/赖氨酸丰富的NLS介导的RelB的结合importin α 5和α 6和随后的蛋白质的核转位。此外，我们表明，核进口的p52/RelB异源二聚体介导的NLS的RelB。此外，我们发现p52的NLS介导p52/p65异源二聚体的核输入。(c)2008年爱思唯尔公司All rights reserved.
In resting cells NF-kappa B transcription factors are retained in the cytoplasm as latent inactive complexes, until they are activated and rapidly transported into the nucleus. We show that all NF-kappa B proteins are imported into the nucleus via a subset of importin a isoforms. Our data indicate that the NF-kappa B components of the classical and alternative pathways have somewhat different specifities to importin a molecules. Based on the results from binding experiments of in vitro-translated and Sendai virus infection-induced or TNF-alpha-stimulated endogenous NF-kappa B proteins, it can be predicted that the specifity of NF-kappa B proteins to importin alpha molecules is different and changes upon the composition of the imported dimer. p52 protein binds directly to importin alpha 3, alpha 4, alpha 5 and alpha 6 and c-Rel binds to importin alpha 5, alpha 6 and alpha 7 via a previously described monopartite nuclear localization signals (NLSs). Here we show that RelB, instead, has a bipartite arginine/lysine-rich NLS that mediates the binding of RelB to importin alpha 5 and alpha 6 and subsequent nuclear translocation of the protein. Moreover, we show that the nuclear import of p52/RelB heterodimers is mediated exclusively by the NLS of RelB. In addition, we found that the NLS of p52 mediates the nuclear import of p52/p65 heterodimers. (c) 2008 Elsevier Inc. All rights reserved.