Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation

Sari Kurki, Karita Peltonen, Leena Latonen, Taija M. Kiviharju, Paivi M. Ojala, David Meek, Marikki Laiho

    Research output: Contribution to journalArticle

    300 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)465-475
    Number of pages11
    JournalCancer Cell
    Volume5
    Issue number5
    DOIs
    Publication statusPublished - May 2004

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    Tumor Suppressor Protein p53
    Cyclins
    Nuclear Proteins
    Kaposi's Sarcoma
    Phosphoproteins
    RNA Interference
    Ribosomes
    Proteins
    Viruses

    Cite this

    Kurki, S., Peltonen, K., Latonen, L., Kiviharju, T. M., Ojala, P. M., Meek, D., & Laiho, M. (2004). Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation. Cancer Cell, 5(5), 465-475. https://doi.org/10.1016/S1535-6108(04)00110-2
    Kurki, Sari ; Peltonen, Karita ; Latonen, Leena ; Kiviharju, Taija M. ; Ojala, Paivi M. ; Meek, David ; Laiho, Marikki. / Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation. In: Cancer Cell. 2004 ; Vol. 5, No. 5. pp. 465-475.
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    abstract = "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.",
    author = "Sari Kurki and Karita Peltonen and Leena Latonen and Kiviharju, {Taija M.} and Ojala, {Paivi M.} and David Meek and Marikki Laiho",
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    year = "2004",
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    Kurki, S, Peltonen, K, Latonen, L, Kiviharju, TM, Ojala, PM, Meek, D & Laiho, M 2004, 'Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation', Cancer Cell, vol. 5, no. 5, pp. 465-475. https://doi.org/10.1016/S1535-6108(04)00110-2

    Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation. / Kurki, Sari; Peltonen, Karita; Latonen, Leena; Kiviharju, Taija M.; Ojala, Paivi M.; Meek, David; Laiho, Marikki.

    In: Cancer Cell, Vol. 5, No. 5, 05.2004, p. 465-475.

    Research output: Contribution to journalArticle

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    AU - Kurki, Sari

    AU - Peltonen, Karita

    AU - Latonen, Leena

    AU - Kiviharju, Taija M.

    AU - Ojala, Paivi M.

    AU - Meek, David

    AU - Laiho, Marikki

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    AB - 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.

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