N-Myc-Interacting Protein Negatively Regulates TNF-α-Induced NF-κB Transcriptional Activity by Sequestering NF-κB/p65 in the Cytoplasm

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...

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Bibliographic Details
Published in:Scientific reports 2017-11, Vol.7 (1), p.14579-14, Article 14579
Main Authors: Hou, Jingjing, Jiang, Shihao, Zhao, Jiabao, Zhu, Dong, Zhao, Xinmeng, Cai, Jian-chun, Zhang, Si Qing
Format: Article
Language:English
Subjects:
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13/2
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96/21
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Apoptosis
Cytoplasm
Cytoplasm - metabolism
HeLa Cells
Humanities and Social Sciences
Humans
Interferon
Interleukin 6
Interleukin-6 - metabolism
Intracellular Signaling Peptides and Proteins - metabolism
multidisciplinary
Myc protein
NF-kappa B - metabolism
NF-κB protein
Nuclear transport
Proto-Oncogene Proteins c-myc - metabolism
Science
Science (multidisciplinary)
Signal Transduction
Transcription
Transcription Factor RelA - metabolism
Transcription, Genetic
Translocation
Tumor cells
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-α
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-15074-5