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EBP1 is a nucleolar growth-regulating protein that is part of pre-ribosomal ribonucleoprotein complexes

Oncogene volume 23, pages 4454–4465 (2004)Cite this article

Abstract

EBP1 was identified as a protein that interacts with the ErbB-3 receptor and possibly contributes to transducing growth regulatory signals. The existence of EBP1 homologs across species from simple eukaryotes to humans and its wide tissue expression pattern suggest that EBP1 acts as a general signaling molecule. We provide evidence that EBP1 is localized to the cytoplasm and to the nucleolus, and that its nucleolar localization requires amino-acid sequences present at both the amino- and carboxy-terminus of the molecule. We also show that EBP1 overexpression inhibits proliferation of human fibroblasts, and that this effect is linked to its nucleolar localization. Using mass spectrometry we demonstrate that EBP1 is part of ribonucleoprotein complexes and associates with different rRNA species. It is becoming clear that cell growth and proliferation are actively coordinated with rRNA processing and ribosome assembly. Our findings indicate that EBP1 is a nucleolar growth-regulating protein, and we propose that it could represent a new link between ribosome biosynthesis and cell proliferation.

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Acknowledgements

We thank Emanuela Colombo for the anti-NPM antibodies. We acknowledge Pietro Transidico for confocal microscope analysis, and Ivan Muradore for FACS analysis and IEO-IFOM sequencing unit. This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC), Consiglio nazionale delle Ricerche (CNR), Fondazione Italiana per la Ricerca sul Cancro (FIRC) and Telethon to GFD. MS and MD were supported by fellowships from FIRC.

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  1. European Institute of Oncology, 435 Via Ripamonti, Milan, 20141, Italy

    Massimo Squatrito, Monica Mancino, Maddalena Donzelli, Liliana B Areces & Giulio F Draetta

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  1. Massimo Squatrito
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  2. Monica Mancino
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Correspondence to Giulio F Draetta.

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Supplementary information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Squatrito, M., Mancino, M., Donzelli, M. et al. EBP1 is a nucleolar growth-regulating protein that is part of pre-ribosomal ribonucleoprotein complexes. Oncogene 23, 4454–4465 (2004). https://doi.org/10.1038/sj.onc.1207579

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