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Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18794-9. doi: 10.1073/pnas.0806879105. Epub 2008 Nov 24.

Nucleophosmin interacts directly with c-Myc and controls c-Myc-induced hyperproliferation and transformation.

Author information

1
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232-2175, USA.

Abstract

The transcription factor c-Myc is essential for cellular proliferation and is one of the most frequently activated oncogenes, but the molecular mechanism mediating its critical role in transformation is unclear. Like c-Myc, multifunctional nucleophosmin (NPM) is tightly regulated during proliferation and is overexpressed in several different types of cancer. Overexpression of NPM enhances proliferation and oncogene-mediated transformation, but the mechanism mediating these effects is unknown. We examined whether NPM stimulates proliferation and transformation by affecting c-Myc. Here, we show that NPM is essential for the activities of oncogenic c-Myc and that overexpressed NPM dramatically stimulates c-Myc-induced hyperproliferation and transformation. Endogenous and exogenous NPM directly interact with c-Myc and regulate the expression of endogenous c-Myc target genes at the promoter. Therefore, NPM is a key cofactor for the transforming activity of c-Myc and the interaction with c-Myc may mediate the enhancement of proliferation and transformation induced by NPM overexppression.

PMID:
19033198
PMCID:
PMC2596228
DOI:
10.1073/pnas.0806879105
[Indexed for MEDLINE]
Free PMC Article

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