Oscillations in NF-κB signaling control the dynamics of gene expression
Oscillations in NF-κB signaling control the dynamics of gene expression
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DOI：
10.1126/science.1099962
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发表时间：
2004-10-22
期刊：
影响因子：
56.9
通讯作者：
White, MRH
中科院分区：
文献类型：
--
作者：
Nelson, DE;Ihekwaba, AEC;White, MRH
通过转录因子核因子κ B（NF-κ B）的信号传导涉及其从胞质溶胶中的抑制剂κ B（IkappaB）释放，随后易位到细胞核中。NF-κ B对IkappaB α转录的调节代表了一个延迟的负反馈环，该环驱动NF-κ B易位中的振荡。NF-kappaB（RelA）定位的单细胞延时成像带计算模型显示，细胞刺激后的异步振荡频率随着IkappaB α转录的增加而降低。靶基因的转录依赖于振荡持续性，涉及RelA磷酸化和去磷酸化的循环。因此，NF-κ B信号传导的功能结果可能取决于振荡的数量、周期和振幅。
Signaling by the transcription factor nuclear factor kappa B (NF-kappaB) involves its release from inhibitor kappa B (IkappaB) in the cytosol, followed by translocation into the nucleus. NF-kappaB regulation Of IkappaBalpha transcription represents a delayed negative feedback loop that drives oscillations in NF-kappaB translocation. Single-cell time-lapse imaging band computational modeling of NF-kappaB (RelA) localization showed asynchronous oscillations following cell stimulation that decreased in frequency with increased IkappaBalpha transcription. Transcription of target genes depended on oscillation persistence, involving cycles of RelA phosphorytation and dephosphorylation. The functional consequences of NF-kappaB signaling may thus depend on number, period, and amplitude of oscillations.