Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

N-Myc and STAT Interactor (NMI)

  • Brandon J. Metge
  • Hawley C. Pruitt
  • Lalita A. Shevde
  • Rajeev S. SamantEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101778


Historical Background

N-myc interactor, NMI, was first characterized as an interactor of c-Myc and n-Myc using a yeast two-hybrid screen. Since its initial discovery, NMI has been studied for its roles in viral pathologies and more extensively for its role in cancer progression. However, literature describing the role of NMI function in normal physiology is relatively unknown aside from inferences from its roles in various pathologies. NMI is a protein mostly studied for its associations with known transcription factors. In humans, expression profiling has determined that NMI is expressed in all fetal tissues except in the brain and primarily in the adult spleen, liver, and kidneys. The human NMI gene is located on chromosome 2q23 and contains three exons that can form four alternatively spliced mRNA transcripts; two with no retained introns code for protein products (Bao and Zervos 1996). NMI’s expression is largely...
This is a preview of subscription content, log in to check access.



NIH R01CA194048 grant to R.S.S.


  1. Bannasch D, Weis I, Schwab M. Nmi protein interacts with regions that differ between MycN and Myc and is localized in the cytoplasm of neuroblastoma cells in contrast to nuclear MycN. Oncogene. 1999;18(48):6810–7.CrossRefPubMedGoogle Scholar
  2. Bao J, Zervos AS. Isolation and characterization of Nmi, a novel partner of Myc proteins. Oncogene. 1996;12(10):2171–6.PubMedGoogle Scholar
  3. Cheng W, et al. Severe acute respiratory syndrome coronavirus protein 6 mediates ubiquitin-dependent proteosomal degradation of N-Myc (and STAT) interactor. Virol Sin. 2015;30(2):153–61.CrossRefPubMedGoogle Scholar
  4. Devine DJ, et al. Loss of N-Myc interactor promotes epithelial-mesenchymal transition by activation of TGF-beta/SMAD signaling. Oncogene. 2014;33(20):2620–8.CrossRefPubMedGoogle Scholar
  5. Fillmore RA, et al. Nmi (N-Myc interactor) inhibits Wnt/beta-catenin signaling and retards tumor growth. Int J Cancer. 2009;125(3):556–64.CrossRefPubMedGoogle Scholar
  6. Hou J, et al. N-Myc-interacting protein (NMI) negatively regulates epithelial-mesenchymal transition by inhibiting the acetylation of NF-kappaB/p65. Cancer Lett. 2016;376(1):22–33.CrossRefPubMedGoogle Scholar
  7. Hu X, et al. N-Myc interactor inhibits prototype foamy virus by sequestering viral Tas protein in the cytoplasm. J Virol. 2014;88(12):7036–44.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Jung HH, et al. STAT1 and Nmi are downstream targets of Ets-1 transcription factor in MCF-7 human breast cancer cell. FEBS Lett. 2005;579(18):3941–6.CrossRefPubMedGoogle Scholar
  9. Li H, Lee TH, Avraham H. A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer. J Biol Chem. 2002;277(23):20965–73.CrossRefPubMedGoogle Scholar
  10. Li Z, et al. NMI mediates transcription-independent ARF regulation in response to cellular stresses. Mol Biol Cell. 2012;23(23):4635–46.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Meng D, et al. High expression of N-myc (and STAT) interactor predicts poor prognosis and promotes tumor growth in human glioblastoma. Oncotarget. 2015;6(7):4901–19.CrossRefPubMedGoogle Scholar
  12. Metge BJ, et al. N-Myc and STAT Interactor regulates autophagy and chemosensitivity in breast cancer cells. Sci Report. 2015;5:11995.CrossRefGoogle Scholar
  13. Nagel S, et al. Transcriptional deregulation of oncogenic myocyte enhancer factor 2C in T-cell acute lymphoblastic leukemia. Leuk Lymphoma. 2011;52(2):290–7.CrossRefPubMedGoogle Scholar
  14. Rostas 3rd JW, et al. MicroRNA-29 negatively regulates EMT regulator N-myc interactor in breast cancer. Mol Cancer. 2014;13:200.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Saito Y, et al. Nmi interacts with Hsp105beta and enhances the Hsp105beta-mediated Hsp70 expression. Exp Cell Res. 2014;327(1):163–70.CrossRefPubMedGoogle Scholar
  16. Schlierf B, et al. The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi. J Mol Biol. 2005;353(5):1033–42.CrossRefPubMedGoogle Scholar
  17. Wang J, et al. A critical role of N-myc and STAT interactor (Nmi) in foot-and-mouth disease virus (FMDV) 2C-induced apoptosis. Virus Res. 2012;170(1–2):59–65.CrossRefPubMedGoogle Scholar
  18. Wang J, et al. Negative regulation of Nmi on virus-triggered type I IFN production by targeting IRF7. J Immunol. 2013;191(6):3393–9.CrossRefPubMedGoogle Scholar
  19. Zhang K, Zheng G, Yang YC. Stability of Nmi protein is controlled by its association with Tip60. Mol Cell Biochem. 2007;303(1–2):1–8.PubMedGoogle Scholar
  20. Zhou X, et al. Interferon-alpha induces nmi-IFP35 heterodimeric complex formation that is affected by the phosphorylation of IFP35. J Biol Chem. 2000;275(28):21364–71.CrossRefPubMedGoogle Scholar
  21. Zhu M, et al. Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling. Cell. 1999;96(1):121–30.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Brandon J. Metge
    • 1
  • Hawley C. Pruitt
    • 1
  • Lalita A. Shevde
    • 2
  • Rajeev S. Samant
    • 1
    • 3
    Email author
  1. 1.Division of Molecular and Cellular Pathology, Department of PathologyUniversity of Alabama at Birmingham, Wallace Tumor InstituteBirminghamUSA
  2. 2.Division of Molecular and Cellular Pathology, Department of Pathology and Comprehensive Cancer CenterUniversity of Alabama at Birmingham, Wallace Tumor InstituteBirminghamUSA
  3. 3.Department of Pathology and Comprehensive Cancer CenterThe University of AlabamaBirminghamUSA