Multiple roles of the NF-κB signaling pathway regulated by coupled negative feedback circuits
Multiple roles of the NF-κB signaling pathway regulated by coupled negative feedback circuits
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DOI：
10.1096/fj.09-130369
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发表时间：
2009-09-01
期刊：
影响因子：
4.8
通讯作者：
Cho, Kwang-Hyun
中科院分区：
文献类型：
--
作者：
Kim, Dongsan;Kolch, Walter;Cho, Kwang-Hyun
NF-κ B信号通路可以根据特定的细胞环境和细胞类型发挥多种功能作用。即使在相同的细胞克隆中，该途径也可以显示不同的动力学和表型特性。据信，控制NF-κ B信号通路的复杂网络可以产生这些多样的，有时是模糊的现象。然而，我们注意到NF-κ B信号通路的动力学是高度随机的，并且NF-κ B信号通路包含由I κ B同种型蛋白，特别是I κ B α和I κ B α形成的多个负反馈回路。考虑到拓扑结构的相似性，它们的功能作用似乎是多余的，提出了为什么需要存在不同类型的I κ B同种型的问题。从广泛的随机模拟NF-κ B信号通路，我们发现，每个I κ B亚型实际上进行了不同的调节作用，通过自己的负反馈。具体来说，我们的数据表明，I κ B α控制核NF-κ B的动态模式，而I κ B α诱导NF-κ B活动的细胞异质性。这些结果可能会提供一个答案的问题，一个单一的NF-κ B信号通路可以执行多种生物功能，即使在相同的克隆群体。金，D.，Kolch，W.，周，K.- H. NF-κ B B信号通路的多重作用受耦合负反馈回路调节。FASEB J.23，2796-2802（2009）. www.fasebj.org
The NF-kappa B signaling pathway can perform multiple functional roles depending on specific cellular environments and cell types. Even in the same cell clones, the pathway can show different kinetic and phenotypic properties. It is believed that the complex networks controlling the NF-kappa B signaling pathway can generate these diverse and sometimes ambiguous phenomena. We noted, however, that the dynamics of NF-kappa B signaling pathway is highly stochastic and that the NF-kappa B signaling pathway contains multiple negative feedback circuits formed by I kappa B isoform proteins, I kappa B alpha and I kappa B epsilon in particular. Considering the topological similarity, their functional roles seem to be redundant, raising the question why different types of I kappa B isoforms need to exist. From extensive stochastic simulations of the NF-kappa B signaling pathway, we found that each I kappa B isoform actually conducts a different regulatory role through its own negative feedback. Specifically, our data suggest that I kappa B alpha controls the dynamic patterns of nuclear NF-kappa B, while I kappa B epsilon induces cellular heterogeneity of the NF-kappa B activities. These results may provide an answer to the question of how a single NF-kappa B signaling pathway can perform multiple biological functions even in the same clonal populations.-Kim, D., Kolch, W., Cho, K.-H. Multiple roles of the NF-kappa B signaling pathway regulated by coupled negative feedback circuits. FASEB J. 23, 2796-2802 (2009). www.fasebj.org