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

Oncogene volume 32, pages 1988–1994 (2013)Cite this article

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Abstract

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.

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Acknowledgements

We thank C Pfarr for pCMV14-NPM-Flag vector, S McMahon for pSUPER retro vector, E Lee for the anti-HA (12CA5), W Tansey for pCGN-HA-Myc1-220 and pCGN-HA-Myc221-439 vectors, E Colombo and PG Pelicci for NPM−/−p53−/− MEFs, G Zambetti for ARF−/−p53−/− MEFs, E Ruley for p53−/− MEFs and J Sedivy for c-myc−/− cells. This work was supported by grants RO1 CA109586 and CA125760 from NCI to SRH.

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

    Z Li & S R Hann

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  1. Z Li
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Correspondence to S R Hann.

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Li, Z., Hann, S. Nucleophosmin is essential for c-Myc nucleolar localization and c-Myc-mediated rDNA transcription. Oncogene 32, 1988–1994 (2013). https://doi.org/10.1038/onc.2012.227

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