Identification and characterization of nucleophosmin/B23/numatrin which binds the anti-oncogenic transcription factor IRF-1 and manifests oncogenic activity (original) (raw)

Oncogene volume 15, pages 1275–1281 (1997)Cite this article

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.

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Authors and Affiliations

  1. Department of Immunology, Faculty of Medicine, Tokyo University, Hongo 7-3-1, Bunkyo-ku, 113, Tokyo
    Takeshi Kondo, Tokiko Nagamura-Inoue, Masahito Matsumoto, Tadatsugu Taniguchi & Nobuyuki Tanaka
  2. National Cardiovascular Center Research Institute, Fujishirodai 5, Suita-shi, 565, Osaka, Japan
    Naoto Minamino

Authors

  1. Takeshi Kondo
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  2. Naoto Minamino
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  3. Tokiko Nagamura-Inoue
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  4. Masahito Matsumoto
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  5. Tadatsugu Taniguchi
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  6. Nobuyuki Tanaka
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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

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