核仁蛋白NPM与HDM2相互作用，保护肿瘤抑制蛋白p53免受HDM2介导的降解。
Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation.
作者信息
Kurki Sari, Peltonen Karita, Latonen Leena, Kiviharju Taija M, Ojala Päivi M, Meek David, Laiho Marikki
机构信息
Haartman Institute and Molecular Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, P.O. Box 63, FIN-00014 Helsinki, Helsinki, Finland.
出版信息
Cancer Cell. 2004 May;5(5):465-75. doi: 10.1016/s1535-6108(04)00110-2.
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.
核仁磷酸蛋白（NPM，B23）是一种丰富的核仁磷蛋白，参与核糖体生物合成，并与肿瘤抑制蛋白p53和Rb相互作用。在此我们表明，NPM是一种紫外线损伤反应蛋白，它会发生核质重新分布，并调节p53和HDM2的水平及其相互作用。通过利用RNA干扰方法以及对内源和异位表达蛋白的分析，我们证明NPM与HDM2结合，并作为p53-HDM2相互作用的负调节因子。由卡波西肉瘤病毒K周期蛋白的表达所引发的病毒应激，会导致NPM重新分布、K周期蛋白与NPM结合，以及通过HDM2-p53复合物的解离实现p53稳定化。这些结果证明了HDM2和K周期蛋白与NPM的新关联，并表明NPM通过抑制HDM2而成为p53的关键调控因子。
Zotero 插件