Nucleophosmin regulates the stability and transcriptional activity of p53

Emanuela Colombo, Jean Christophe Marine, Davide Danovi, Brunangelo Falini, Pier Giuseppe Pelicci

Research output: Contribution to journalArticle

386 Citations (Scopus)

Abstract

Nucleophosmin (NPM) is a ubiquitously expressed nucleolar phosphoprotein that continuously shuttles between the nucleus and cytoplasm1. It has been proposed to function in ribosomal protein assembly and transport2, and also as a molecular chaperone that prevents proteins from aggregating in the crowded environment of the nucleolus3. The NPM gene is involved in several tumour-associated chromosome translocations, which have resulted in the formation of fusion proteins that retain the amino terminus of NPM, including NPM-ALK4, NPM-RAR5 and NPM-MLF1 (ref. 6). It is generally thought that the NPM component is not involved in the transforming potential of these fusion proteins7, but instead provides a dimerization interface for the oligomerization and the oncogenic conversion of the various NPM partners (ALK, RAR, MLF1). Here we show that NPM interacts directly with the tumour suppressor p53, regulates the increase in stability and transcriptional activation of p53 after different types of stress, and induces p53-dependent premature senescence on overexpression in diploid fibroblasts. These findings indicate that NPM is a crucial regulator of p53 and suggest that alterations of the NPM function by NPM fusion proteins might lead to deregulation of p53 in tumours.

Original languageEnglish
Pages (from-to)529-533
Number of pages5
JournalNature Cell Biology
Volume4
Issue number7
DOIs
Publication statusPublished - 2002

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nucleophosmin
Neoplasms
Proteins
Molecular Chaperones
Ribosomal Proteins
Phosphoproteins
Dimerization
Diploidy
Transcriptional Activation
Fibroblasts
Chromosomes
Genes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Nucleophosmin regulates the stability and transcriptional activity of p53. / Colombo, Emanuela; Marine, Jean Christophe; Danovi, Davide; Falini, Brunangelo; Pelicci, Pier Giuseppe.

In: Nature Cell Biology, Vol. 4, No. 7, 2002, p. 529-533.

Research output: Contribution to journalArticle

Colombo, Emanuela ; Marine, Jean Christophe ; Danovi, Davide ; Falini, Brunangelo ; Pelicci, Pier Giuseppe. / Nucleophosmin regulates the stability and transcriptional activity of p53. In: Nature Cell Biology. 2002 ; Vol. 4, No. 7. pp. 529-533.
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