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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Stimulated nuclear translocation of NF-κb and shuttling differentially depend on dynein and the dynactin complex
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Stimulated nuclear translocation of NF-κb and shuttling differentially depend on dynein and the dynactin complex

机译:刺激的NF-κb核易位和穿梭差异取决于动力蛋白和动力蛋白复合物

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摘要

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-κB) family. The p65:p50 NF-κB het-erodimer that predominates in many cell types can undergo stimulated movement, following degradation of the IκB inhibitor, as well as shuttling in the absence of stimulation with IκB 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-κB. A differential dependence of these two modes of transport on the dynein molecular motor and dynactin was found. NF-kB 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_1 activation of NF-κB-dependent gene expression showed a dependence on endogenous dynein in a variety of cell types and in response to diverse activating stimuli, suggesting that dynein-dependent transport of NF-κB may be a conserved mechanism in the NF-κB activation pathway and could represent a potential point of regulation.
机译:从细胞质到细胞核的转运是通过核因子κB(NF-κB)家族的转录因子调节基因表达所必需的。在许多细胞类型中占主导地位的p65:p50NF-κB异二聚体可在IκB抑制剂降解后经历刺激的运动,以及在不受IκB结合刺激的情况下穿梭。肌动蛋白复合物的破坏和内源性达因的敲低被用来研究NF-κB刺激和穿梭运动的核转运要求。发现这两种运输方式对动力蛋白分子动力和动力蛋白的依赖性。刺激后,NF-κB使用主动的动力蛋白依赖性运输,而穿梭过程中的易位则由动力蛋白依赖性途径介导的动力蛋白依赖性途径介导,这与促进扩散的过程一致。核易位和NF-κB依赖性基因表达的_1活化表明在多种细胞类型中均依赖内源性达因,并响应多种激活刺激,提示达因蛋白依赖性的NF-κB转运可能是NF中的保守机制。 -κB激活途径,可能代表潜在的调控点。

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