[Identification and analysis of IRF-1 binding protein].
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.
Kondo
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Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007938:Leukemia / Q000209:etiology; D009190:Myelodysplastic Syndromes / Q000209:etiology; D009857:Oncogenes; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D012333:RNA, Messenger