N-Myc-Interacting Protein Negatively Regulates TNF-?-Induced NF-?B Transcriptional Activity by Sequestering NF-?B/p65 in the Cytoplasm.

ABSTRACT: NF-?B is a major regulator of gene transcription involved in immune, inflammation, apoptosis and stress responses. However, the regulation of NF-?B 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-?B activity. We found that NMI negatively regulates TNF-?-induced IL-6 and IL-1? production in HeLa cells. Overexpression of NMI inhibits NF-?B transcriptional activity, in contrast, depletion of NMI by shRNA increases NF-?B transcriptional activity. Mechanistically, NMI associates with NF-?B/p65 and inhibits NF-?B/p65 nuclear translocation and thereby negatively regulates NF-?B/p65 transcriptional activity. Taken together, our results demonstrate that NMI modulates the NF-?B signaling pathway by sequestering NF-?B/p65 in the cytoplasm, resulting in reduced IL-6 and IL-1? production after TNF-? stimulation. Treatment with IFN? in the presence of NMI leads to increased apoptosis in tumor cells. These findings reveal a novel mechanism by which NMI regulates NF-?B activity.

SUBMITTER: Hou J 

PROVIDER: S-EPMC5674077 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature