Kondo T
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1996 Jul;71(4):509-16.
Interferon Regulatory Factor-1 (IRF-1) acts as a transcriptional activator in interferon system and as a tumor suppressor. The loss of functional IRF-1 has been shown in approximately 30% of patients with myelodysplastic syndrome (MDS) and overt leukemia from MDS. Here we report an alternative mechanism of inactivation of IRF-1 activity. We identified an IRF-1 binding protein (IRF-BP). Protein sequencing revealed that IRF-BP was identical to nucleophosmin (NPM), a nucleolar phosphoprotein. Functional analysis showed that IRF-BP inhibited DNA-binding and transcriptional activity of IRF-1. Moreover when we examined several leukemia samples, the level of IRF-BP mRNA was increased. These results are consistent with the hypothesis that IRF-BP binds to IRF-1, and that overexpression of IRF-BP in leukemias leads to escape from IRF-1-regulated growth control. This hypothesis was also supported by the fact that overexpression of IRF-BP in NIH 3T3 cells rendered cells transformed.
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发挥作用，同时也是一种肿瘤抑制因子。在大约30%的骨髓增生异常综合征（MDS）患者以及由MDS发展而来的明显白血病患者中，已发现功能性IRF-1缺失。在此，我们报告一种IRF-1活性失活的替代机制。我们鉴定出一种IRF-1结合蛋白（IRF-BP）。蛋白质测序显示IRF-BP与核磷蛋白（NPM）相同，NPM是一种核仁磷蛋白。功能分析表明，IRF-BP抑制IRF-1的DNA结合和转录活性。此外，当我们检测多个白血病样本时，IRF-BP mRNA水平升高。这些结果与以下假设一致：IRF-BP与IRF-1结合，并且白血病中IRF-BP的过表达导致细胞逃脱IRF-1调控的生长控制。NIH 3T3细胞中IRF-BP的过表达使细胞发生转化这一事实也支持了该假设。
