Oscillation dynamics underlie functional switching of NF-κB for B-cell activation.
Oscillation dynamics underlie functional switching of NF-κB for B-cell activation.
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DOI：
10.1038/npjsba.2016.24
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发表时间：
2016
影响因子：
4
通讯作者：
Okada-Hatakeyama M
中科院分区：
文献类型：
--
作者：
Inoue K;Shinohara H;Behar M;Yumoto N;Tanaka G;Hoffmann A;Aihara K;Okada-Hatakeyama M
转录因子核因子κB （NF-κB）在细胞外刺激下表现出协同开关样激活，随后是长时间的振荡核易位。这些动态对于NF-κB转录机制的激活是重要的，然而，这些动态的协调作用调节的NF-κB活性尚未在系统水平上得到阐明。利用人工重新连接NF-κB信号网络的多种B细胞，我们发现振荡和NF-κB的开关样激活可以被解剖，并且在某些条件下，这两种行为在抗原受体激活时被分离。综合定量实验和数学分析表明，开关激活在NF-κB系统中的功能作用是克服瞬时IKK （i -κB激酶）活性，放大NF-κB的核易位，从而诱导靶基因表达和b细胞活化所必需的NF-κB振荡行为延长。
Transcription factor nuclear factor kappa B (NF-κB) shows cooperative switch-like activation followed by prolonged oscillatory nuclear translocation in response to extracellular stimuli. These dynamics are important for activation of the NF-κB transcriptional machinery, however, NF-κB activity regulated by coordinated actions of these dynamics has not been elucidated at the system level. Using a variety of B cells with artificially rewired NF-κB signaling networks, we show that oscillations and switch-like activation of NF-κB can be dissected and that, under some conditions, these two behaviors are separated upon antigen receptor activation. Comprehensive quantitative experiments and mathematical analysis showed that the functional role of switch activation in the NF-κB system is to overcome transient IKK (IκB kinase) activity to amplify nuclear translocation of NF-κB, thereby inducing the prolonged NF-κB oscillatory behavior necessary for target gene expression and B-cell activation.
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影响因子：
4.6
作者：
Shinohara H;Inoue K;Yumoto N;Nagashima T;Okada-Hatakeyama M
通讯作者：
Okada-Hatakeyama M
影响因子：
9.9
作者：
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作者：
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作者：
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通讯作者：
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影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM