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Hepatocyte odd protein shuttling (HOPS) is a bridging protein in the nucleophosmin-p19Arf network

Oncogene volume 32, pages 3350–3358 (2013)Cite this article

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Abstract

Nucleophosmin (NPM), a ubiquitously and abundantly expressed protein, occurs in the nucleolus, shuttling between the nucleoplasm and cytoplasm. The NPM gene is mutated in almost 30% of human acute myeloid leukemia cells. NPM interacts with p53 and p19Arf, directs localization of p19Arf in the nucleolus and protects the latter from degradation. Hepatocyte odd protein shuttling (HOPS) is also a ubiquitously expressed protein that moves between the nucleus and cytoplasm. Within the nucleus of resting cells, HOPS overexpression causes cell cycle arrest in G0/G1. HOPS knockdown causes centrosome hyperamplification leading to multinucleated cells and the formation of micronuclei. We demonstrate a direct interaction of HOPS with NPM and p19Arf, resulting in a functionally active trimeric complex. NPM appeared to regulate HOPS half-life, which, in turn, stabilized p19Arf and controlled its localization in the nucleolus. These findings suggest that HOPS acts as a functional bridge in the interaction between NPM and p19Arf, providing new mechanistic insight into how NPM and p19Arf will oppose tumor cell proliferation.

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Acknowledgements

We thank Paolo Puccetti and Stefano Brancorsini for the critical reading of the manuscript, Silvano Pagnotta for technical assistance. This study was supported by grants from the Associazione Umbra Contro il Cancro (AUCC), Fondazione Guido Berlucchi, the Associazione Italiana Ricerca sul Cancro (AIRC), Only the Brave Foundation and Fondazione Cassa di Risparmio di Perugia. GS is recipient of a PRIN Project n. 2008BH7KA2_003. DB, CB and DP are recipient of the AUCC fellowship program.

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Author notes

  1. M Castelli and S Pieroni: These authors contributed equally to this work.

  2. M A Della Fazia and G Servillo: These authors share senior authorship.

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy

    M Castelli, S Pieroni, C Brunacci, D Piobbico, D Bartoli, M M Bellet, M A Della Fazia & G Servillo

  2. Department of Experimental Oncology, Instituto Europeo di Oncologia, Milan, Italy

    E Colombo & P G Pelicci

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  1. M Castelli
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  2. S Pieroni
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Correspondence to G Servillo.

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Castelli, M., Pieroni, S., Brunacci, C. et al. Hepatocyte odd protein shuttling (HOPS) is a bridging protein in the nucleophosmin-p19Arf network. Oncogene 32, 3350–3358 (2013). https://doi.org/10.1038/onc.2012.353

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