N-Myc-Interacting Protein Negatively Regulates TNF-α-Induced NF-κB Transcriptional Activity by Sequestering NF-κB/p65 in the Cytoplasm.
N-Myc-Interacting Protein Negatively Regulates TNF-α-Induced NF-κB Transcriptional Activity by Sequestering NF-κB/p65 in the Cytoplasm.
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N-Myc 相互作用蛋白通过在细胞质中隔离 NF-kappa B/p65 负调节 TNF-α 诱导的 NF-kappa B 转录活性
DOI：
10.1038/s41598-017-15074-5
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发表时间：
2017-11-06
影响因子：
4.6
通讯作者：
Zhang SQ
中科院分区：
文献类型：
--
作者：
Hou J;Jiang S;Zhao J;Zhu D;Zhao X;Cai JC;Zhang SQ
NF-κB是参与免疫、炎症、细胞凋亡和应激反应的主要基因转录调控因子。然而，NF-κB的调控尚不完全清楚。在这里，我们报道了N-Myc和STATs相互作用因子（NMI），一种ifn诱导蛋白，是NF-κB活性的重要负调节因子。我们发现NMI负调控TNF-α-诱导的HeLa细胞IL-6和IL-1β的产生。NMI过表达会抑制NF-κB的转录活性，而shRNA缺失NMI则会增加NF-κB的转录活性。在机制上，NMI与NF-κB/p65相关，抑制NF-κB/p65核易位，从而负向调节NF-κB/p65转录活性。综上所述，我们的研究结果表明，NMI通过在细胞质中隔离NF-κB/p65来调节NF-κB信号通路，导致TNF-α刺激后IL-6和IL-1β的产生减少。在NMI存在的情况下用IFNα治疗可导致肿瘤细胞凋亡增加。这些发现揭示了NMI调控NF-κB活性的新机制。
NF-κB is a major regulator of gene transcription involved in immune, inflammation, apoptosis and stress responses. However, the regulation of NF-κB is not completely understood. Here, we report that the N-Myc and STATs Interactor (NMI), an IFN-inducible protein, is an important negative regulator of NF-κB activity. We found that NMI negatively regulates TNF-α-induced IL-6 and IL-1β production in HeLa cells. Overexpression of NMI inhibits NF-κB transcriptional activity, in contrast, depletion of NMI by shRNA increases NF-κB transcriptional activity. Mechanistically, NMI associates with NF-κB/p65 and inhibits NF-κB/p65 nuclear translocation and thereby negatively regulates NF-κB/p65 transcriptional activity. Taken together, our results demonstrate that NMI modulates the NF-κB signaling pathway by sequestering NF-κB/p65 in the cytoplasm, resulting in reduced IL-6 and IL-1β production after TNF-α stimulation. Treatment with IFNα in the presence of NMI leads to increased apoptosis in tumor cells. These findings reveal a novel mechanism by which NMI regulates NF-κB activity.
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影响因子：
15.9
作者：
Baldwin, AS
通讯作者：
Baldwin, AS
影响因子：
1.7
作者：
Chung, Jun Chul;Oh, Mi Jung;Bae, Chang Dae
通讯作者：
Bae, Chang Dae
影响因子：
50.3
作者：
Lee H;Herrmann A;Deng JH;Kujawski M;Niu G;Li Z;Forman S;Jove R;Pardoll DM;Yu H
通讯作者：
Yu H
NMI 介导转录独立的 ARF 调节以应对细胞应激
影响因子：
3.3
作者：
Li Z;Hou J;Sun L;Wen T;Wang L;Zhao X;Xie Q;Zhang SQ
通讯作者：
Zhang SQ
DOI：
10.1083/jcb.145.7.1471
发表时间：
1999-06-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Heyninck K;De Valck D;Vanden Berghe W;Van Criekinge W;Contreras R;Fiers W;Haegeman G;Beyaert R
通讯作者：
Beyaert R