Identification and characterization of nucleophosmin/B23/numatrin which binds the anti-oncogenic transcription factor IRF-1 and manifests oncogenic activity
Identification and characterization of nucleophosmin/B23/numatrin which binds the anti-oncogenic transcription factor IRF-1 and manifests oncogenic activity
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DOI：
10.1038/sj.onc.1201286
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发表时间：
1997-09-11
期刊：
影响因子：
8
通讯作者：
Tanaka, N
中科院分区：
文献类型：
--
作者：
Kondo, T;Minamino, N;Tanaka, N
干扰素调节因子-1（IRF-1）在干扰素系统中作为转录激活因子和肿瘤抑制因子。在大量骨髓增生异常综合征（MDS）和白血病患者中观察到功能性IRF-1的丧失，表明IRF-1在人类肿瘤抑制中可能具有关键作用。在这里，我们报告了一种替代机制，IRF-1可能被灭活。我们纯化了IRF-1缔合分子，其被揭示为与核因子核磷蛋白（NPM）/B23/numatrin相同。功能分析表明，NPM抑制IRF-1的DNA结合和转录活性。此外，NPM在一些临床白血病样品和人源性白血病细胞系中过表达。最后，NPM在NIH 3 T3细胞中的过表达导致恶性转化。这些结果表明，NPM可能参与失活IRF-1依赖的抗癌监测在人类癌症的发展。
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.