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

• 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: 13/109; 13/2; 13/89; 38/1; 38/90; 45/23; 631/80/82/23; 631/80/86/2368; 82/80; 96/21; 96/95; 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-15074-5

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.