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, Päivi M. Ojala, David Meek, Marikki Laiho

Research output: Contribution to journalArticle

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 (US)
Pages (from-to)465-475
Number of pages11
JournalCancer Cell
Volume5
Issue number5
DOIs
StatePublished - May 2004
Externally publishedYes

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

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

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, Päivi M.; Meek, David; Laiho, Marikki.

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

Research output: Contribution to journalArticle

Kurki, Sari ; Peltonen, Karita ; Latonen, Leena ; Kiviharju, Taija M. ; Ojala, Päivi 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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AU - Meek, David

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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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