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首页> 外文期刊>Molecular and Cellular Biology >Generation and Activation of Multiple Dimeric Transcription Factors within the NF-κB Signaling System
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Generation and Activation of Multiple Dimeric Transcription Factors within the NF-κB Signaling System

机译：NF-κB信号系统内多个二聚体转录因子的产生和激活

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The NF-κB signaling pathway regulates the activity of multiple dimeric transcription factors that are generated from five distinct monomers. The availabilities of specific dimers are regulated during cell differentiation and organ development and determine the cell's responsiveness to inflammatory or developmental signals. An altered dimer distribution is a hallmark of many chronic diseases. Here, we reveal that the cellular processes that generate different NF-κB dimers are highly connected through multiple cross-regulatory mechanisms. First, we find that steady-state expression of RelB is regulated by the canonical pathway and constitutive RelA activity. Indeed, synthesis control of RelB is the major determinant of noncanonical NF-κB dimer activation. Second, processing, not synthesis, of p100 and p105 is mechanistically linked via competitive dimerization with a limited pool of RelA and RelB. This homeostatic cross-regulatory mechanism determines the availability of the p50- and p52-containing dimers and also of the noncanonical IκB p100. Our results inform a wiring diagram to delineate NF-κB dimer formation that emphasizes that inflammatory and developmental signaling cannot be considered separately but are highly interconnected.
机译：NF-κB信号通路调节由五个不同单体产生的多个二聚体转录因子的活性。特定二聚体的可用性在细胞分化和器官发育过程中受到调节，并决定细胞对炎症或发育信号的反应能力。二聚体分布的改变是许多慢性疾病的标志。在这里，我们揭示了产生不同NF-κB二聚体的细胞过程通过多种交叉调节机制高度连接。首先，我们发现RelB的稳态表达受规范途径和组成型RelA活性的调节。实际上，RelB的合成控制是非经典NF-κB二聚体激活的主要决定因素。第二，p100和p105的加工而非合成是通过竞争性二聚作用与有限的RelA和RelB进行机械连接的。这种稳态交叉调节机制决定了含p50和p52的二聚体以及非经典IκBp100的可用性。我们的结果告知了一个描绘NF-κB二聚体形成的接线图，该图强调了炎症信号和发育信号不能分开考虑，而是高度相互联系。

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