Nucleophosmin (NPM, B23) is an abundant nucleolar phosphoprotein involved in ribosome biogenesis, and interacts with tumor suppressor proteins p53 and Rb. Here we show that NPM is a UV damage response protein that undergoes nucleoplasmic redistribution and regulates p53 and HDM2 levels and their interaction. By utilizing RNAi approaches and analyses of endogenous and ectopically expressed proteins, we demonstrate that NPM binds HDM2 and acts as a negative regulator of p53-HDM2 interaction. Viral stress, enforced by expression of Kaposi's sarcoma virus K cyclin, causes NPM redistribution, K cyclin-NPM association, and p53 stabilization by dissociation of HDM2-p53 complexes. The results demonstrate novel associations of HDM2 and K cyclin with NPM and implicate NPM as a crucial controller of p53 through inhibition of HDM2.

中文翻译：

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核仁蛋白NPM与HDM2相互作用，并保护肿瘤抑制蛋白p53免受HDM2介导的降解。

核蛋白（NPM，B23）是一种参与核糖体生物发生的丰富核仁磷蛋白，可与肿瘤抑制蛋白p53和Rb相互作用。在这里，我们显示NPM是一种紫外线损伤反应蛋白，它经历核质的重新分布并调节p53和HDM2的水平及其相互作用。通过利用RNA干扰方法和内源性和异位表达的蛋白质的分析，我们证明NPM结合HDM2，并充当p53-HDM2相互作用的负调节剂。通过卡波西氏肉瘤病毒K细胞周期蛋白的表达而引起的病毒应激会导致HDM2-p53复合体解离，从而引起NPM重新分布，K细胞周期蛋白-NPM缔合和p53稳定。结果表明HDM2和K细胞周期蛋白与NPM的新型关联，并通过抑制HDM2暗示NPM作为p53的关键控制者。