Regulation of NF-κB Oscillation by Nuclear Transport: Mechanisms Determining the Persistency and Frequency of Oscillation.
Regulation of NF-κB Oscillation by Nuclear Transport: Mechanisms Determining the Persistency and Frequency of Oscillation.
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DOI：
10.1371/journal.pone.0127633
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ichikawa K
中科院分区：
文献类型：
--
作者：
Ohshima D;Ichikawa K
转录因子NF-κB在细胞质和细胞核之间穿梭，导致核内NF-κB（NF-κBn）的振荡。NF-κBn的振荡模式与基因表达谱的调节有关。利用计算模型，我们先前报道了空间参数，如扩散系数、核质体积比、通过核膜的转运以及IκB蛋白的翻译位点，改变了NF-κBn的振荡模式。在随后的报告中，我们阐明了NF-κBn的“重置”（NF-κB恢复到原始水平）和IκB在细胞质中的“储存库”的重要性。当IκB的扩散系数较大时，储存在离核较远位置的IκB扩散回核并“重置”NF-κBn。在此，我们报道了通过核转运调节NF-κBn振荡持续时间和频率的机制。在我们的时空计算模型中测试的核运输的四个参数中，IκB mRNA从细胞核的输出调节了振荡的持续性。IκB的输入调节了振荡频率。剩下的两个参数，NF-κB输入和输出到细胞核，几乎没有影响的持久性或频率。我们的分析表明，IκB mRNA的输出较少，使NF-κBn能够转录更多的IκB mRNA，这些mRNA保留在细胞核中，随后输出到细胞质中，在细胞质中合成大量的IκB以“重置”NF-κBn并驱动持续的振荡。另一方面，IκB的大量输入导致NF-κB流入和流出细胞核的增加，导致振荡频率增加。我们的研究揭示了核转运在调节NF-κBn振荡模式中的重要性。
The activated transcription factor NF-κB shuttles between the cytoplasm and the nucleus resulting in the oscillation of nuclear NF-κB (NF-κBn). The oscillation pattern of NF-κBn is implicated in the regulation of gene expression profiles. Using computational models, we previously reported that spatial parameters, such as the diffusion coefficient, nuclear to cytoplasmic volume ratio, transport through the nuclear envelope, and the loci of translation of IκB protein, modified the oscillation pattern of NF-κBn. In a subsequent report, we elucidated the importance of the “reset” of NF-κBn (returning of NF-κB to the original level) and of a “reservoir” of IκB in the cytoplasm. When the diffusion coefficient of IκB was large, IκB stored at a distant location from the nucleus diffused back to the nucleus and “reset” NF-κBn. Herein, we report mechanisms that regulate the persistency and frequency of NF-κBn oscillation by nuclear transport. Among the four parameters of nuclear transport tested in our spatio-temporal computational model, the export of IκB mRNA from the nucleus regulated the persistency of oscillation. The import of IκB to the nucleus regulated the frequency of oscillation. The remaining two parameters, import and export of NF-κB to and from the nucleus, had virtually no effect on the persistency or frequency. Our analyses revealed that lesser export of IκB mRNA allowed NF-κBn to transcript greater amounts of IκB mRNA, which was retained in the nucleus, and was subsequently exported to the cytoplasm, where large amounts of IκB were synthesized to “reset” NF-κBn and drove the persistent oscillation. On the other hand, import of greater amounts of IκB led to an increase in the influx and the efflux of NF-κB to and from the nucleus, resulting in an increase in the oscillation frequency. Our study revealed the importance of nuclear transport in regulating the oscillation pattern of NF-κBn.
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DOI：
10.1016/j.bbrc.2008.06.128
发表时间：
2008-09-26
影响因子：
3.1
作者：
Takahashi, Nozomi;van Kilsdonk, Jeroen W. J.;Swart, Guido W. M.
通讯作者：
Swart, Guido W. M.
NF-kappa B信号传导中振荡途径之间的相互作用。
影响因子：
--
作者：
Wang Y;Paszek P;Horton CA;Kell DB;White MR;Broomhead DS;Muldoon MR
通讯作者：
Muldoon MR
影响因子：
4.8
作者：
Kim, Dongsan;Kolch, Walter;Cho, Kwang-Hyun
通讯作者：
Cho, Kwang-Hyun
DOI：
10.1016/j.bbrc.2009.10.154
发表时间：
2010-01-01
影响因子：
3.1
作者：
Kim, Sung Young;Ryu, Sung Jin;Park, Sang Chul
通讯作者：
Park, Sang Chul
DOI：
10.1177/0037549703040943
发表时间：
2003-12-01
影响因子：
1.6
作者：
Cho, KH;Shin, SY;Wolkenhauer, O
通讯作者：
Wolkenhauer, O