Abstract
Interferon regulatory factor-1 (IRF-1) acts as a transcriptional activator in the interferon system and as a tumor suppressor. The loss of functional IRF-1 has been observed in a significant number of patients with myelodysplastic syndrome (MDS) and leukemia, suggesting a potentially critical role of IRF-1 in human oncostasis. Here we report an alternative mechanism by which IRF-1 may be inactivated. We purified an IRF-1 association molecule which was revealed to be identical to a nuclear factor nucleophosmin (NPM)/B23/numatrin. Functional analysis showed that NPM inhibited the DNA-binding and transcriptional activity of IRF-1. Moreover, NPM was overexpressed in several clinical leukemia samples and human-derived leukemia cell lines. Finally, overexpression of NPM in NIH3T3 cells resulted in malignant transformation. These results suggest the possible involvement of NPM in inactivating IRF-1-dependent anti-oncogenic surveillance in human cancer development.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kondo, T., Minamino, N., Nagamura-Inoue, T. et al. Identification and characterization of nucleophosmin/B23/numatrin which binds the anti-oncogenic transcription factor IRF-1 and manifests oncogenic activity. Oncogene 15, 1275–1281 (1997). https://doi.org/10.1038/sj.onc.1201286
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201286
Keywords
This article is cited by
-
NPM promotes hepatotoxin-induced fibrosis by inhibiting ROS-induced apoptosis of hepatic stellate cells and upregulating lncMIAT-induced TGF-β2
Cell Death & Disease (2023)
-
NPM1 alternative transcripts are upregulated in acute myeloid and lymphoblastic leukemia and their expression level affects patient outcome
Journal of Translational Medicine (2018)
-
A polypeptide from the junction region sequence of EWS-FLI1 inhibits Ewing’s sarcoma cells, interacts with the EWS-FLI1 and partner proteins
Scientific Reports (2017)
-
A novel mechanism of post-translational modulation of HMGA functions by the histone chaperone nucleophosmin
Scientific Reports (2015)
-
Emerging roles of nucleolar and ribosomal proteins in cancer, development, and aging
Cellular and Molecular Life Sciences (2015)