Nucleophosmin is essential for c-Myc nucleolar localization and c-Myc-mediated rDNA transcription.

Li Z, Hann SR
Oncogene. 2013 32 (15): 1988-94

PMID: 22665062 · PMCID: PMC3855075 · DOI:10.1038/onc.2012.227

The transcription factor c-Myc has a critical role in cell proliferation and growth. The control of ribosome biogenesis by c-Myc through the regulation of transcription mediated by all three RNA polymerases is essential for c-Myc-driven proliferation. Specifically, in the nucleolus, c-Myc has been shown to be recruited to ribosomal DNA and activate RNA polymerase (pol) I-mediated transcription of ribosomal RNA (rRNA) genes. In addition, c-Myc accumulates in nucleoli upon inhibition of the proteasome, suggesting nucleolar localization also has a role in c-Myc proteolysis. Nucleophosmin (NPM), a predominantly nucleolar protein, is also critical in ribosome biogenesis and, like c-Myc, is found overexpressed in many types of tumors. Previously, we demonstrated that NPM directly interacts with c-Myc and controls c-Myc-induced hyperproliferation and transformation. Here, we show that NPM is necessary for the localization of c-Myc protein to nucleoli, whereas c-Myc nucleolar localization is independent of p53, Mdm2 and ARF. Conversely, high transient NPM expression enhances c-Myc nucleolar localization, leading to increased c-Myc proteolysis. In addition, NPM is necessary for the ability of c-Myc to induce rRNA synthesis in the nucleolus, and constitutive NPM overexpression stimulates c-Myc-mediated rRNA synthesis. Taken together, these results demonstrate an essential role for NPM in c-Myc nucleolar localization and c-Myc-mediated rDNA transcription.

MeSH Terms (12)

Cell Nucleolus Cell Proliferation DNA, Ribosomal Humans Nuclear Proteins Proteasome Endopeptidase Complex Proto-Oncogene Proteins c-mdm2 Proto-Oncogene Proteins c-myc RNA, Ribosomal RNA Polymerase I Transcription, Genetic Tumor Suppressor Protein p53

Connections (1)

This publication is referenced by other Labnodes entities: