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

Li Z, Boone D, Hann SR
Proc Natl Acad Sci U S A. 2008 105 (48): 18794-9

PMID: 19033198 · PMCID: PMC2596228 · DOI:10.1073/pnas.0806879105

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.

MeSH Terms (15)

ADP-Ribosylation Factors Animals Cell Proliferation Cells, Cultured Cell Transformation, Neoplastic Fibroblasts Mice Mice, Knockout Nuclear Proteins Protein Structure, Tertiary Proto-Oncogene Proteins c-mdm2 Proto-Oncogene Proteins c-myc Recombinant Fusion Proteins Transcription, Genetic Tumor Suppressor Protein p53

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