Stimulated nuclear translocation of NF-κB and shuttling differentially depend on dynein and the dynactin complex
Stimulated nuclear translocation of NF-κB and shuttling differentially depend on dynein and the dynactin complex
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DOI：
10.1073/pnas.0806677106
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发表时间：
2009-02-24
影响因子：
11.1
通讯作者：
Meffert, Mollie K.
中科院分区：
文献类型：
--
作者：
Shrum, Cynthia K.;DeFrancisco, Daniel;Meffert, Mollie K.
核因子κ B （nf - κ B）家族的转录因子调控基因表达需要细胞质向细胞核的易位。在许多细胞类型中占主导地位的p65: p50 NF-kappa B异源二聚体可以经历受刺激的运动，随着I kappa B抑制剂的降解，以及在没有I kappa B结合刺激的情况下穿梭。我们利用破坏动力蛋白复合物和敲低内源性动力蛋白来研究NF-kappa b受刺激和穿梭运动的核易位要求。我们发现，这两种运输方式对动力蛋白分子运动和动力蛋白的依赖存在差异。NF-kappa B在刺激后使用主动的动力蛋白依赖转运，而穿梭过程中的转运是由动力蛋白不依赖的途径介导的，该途径可以通过动力蛋白破坏而增强，这与促进扩散的过程一致。NF-kappa B依赖基因表达的核易位和激活在多种细胞类型和对多种激活刺激的反应中显示出对内源性动力蛋白的依赖，这表明NF-kappa B的动力非依赖性转运可能是NF-kappa B激活途径中的一个保守机制，可能是一个潜在的调控点。
Translocation from the cytoplasm to the nucleus is required for the regulation of gene expression by transcription factors of the nuclear factor kappa B (NF-kappa B) family. The p65: p50 NF-kappa B heterodimer that predominates in many cell types can undergo stimulated movement, following degradation of the I kappa B inhibitor, as well as shuttling in the absence of stimulation with I kappa B bound. Disruption of the dynactin complex and knockdown of endogenous dynein were used to investigate the nuclear translocation requirements for stimulated and shuttling movement of NF-kappa B. A differential dependence of these two modes of transport on the dynein molecular motor and dynactin was found. NF-kappa B used active dynein-dependent transport following stimulation while translocation during shuttling was mediated by a dynein-independent pathway that could be potentiated by dynactin disruption, consistent with a process of facilitated diffusion. Nuclear translocation and activation of NF-kappa B-dependent gene expression showed a dependence on endogenous dynein in a variety of cell types and in response to diverse activating stimuli, suggesting that dyneindependent transport of NF-kappa B may be a conserved mechanism in the NF-kappa B activation pathway and could represent a potential point of regulation.