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Molecular and Cellular Biology, May 2006, p. 3798-3809, Vol. 26, No. 10
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.10.3798-3809.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Nucleophosmin Is Essential for Ribosomal Protein L5 Nuclear Export

Yue Yu,1 Leonard B. Maggi Jr.,1 Suzanne N. Brady,1 Anthony J. Apicelli,1 Mu-Shui Dai,2 Hua Lu,2 and Jason D. Weber1*

Department of Internal Medicine, Division of Molecular Oncology, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63110,1 Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health Science University, Portland, Oregon 972012

Received 20 October 2005/ Returned for modification 7 December 2005/ Accepted 24 February 2006

Nucleophosmin (NPM/B23) is a key regulator in the regulation of a number of processes including centrosome duplication, maintenance of genomic integrity, and ribosome biogenesis. While the mechanisms underlying NPM function are largely uncharacterized, NPM loss results in severe dysregulation of developmental and growth-related events. We show that NPM utilizes a conserved CRM1-dependent nuclear export sequence in its amino terminus to enable its shuttling between the nucleolus/nucleus and cytoplasm. In search of NPM trafficking targets, we biochemically purified NPM-bound protein complexes from HeLa cell lysates. Consistent with NPM's proposed role in ribosome biogenesis, we isolated ribosomal protein L5 (rpL5), a known chaperone for the 5S rRNA. Direct interaction of NPM with rpL5 mediated the colocalization of NPM with maturing nuclear 60S ribosomal subunits, as well as newly exported and assembled 80S ribosomes and polysomes. Inhibition of NPM shuttling or loss of NPM blocked the nuclear export of rpL5 and 5S rRNA, resulting in cell cycle arrest and demonstrating that NPM and its nuclear export provide a unique and necessary chaperoning activity to rpL5/5S.

* Corresponding author. Mailing address: Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Campus Box 8069, 660 South Euclid Avenue, St. Louis, MO 63110. Phone: (314) 747-3896. Fax: (314) 747-2797. E-mail: jweber{at}im.wustl.edu.

Molecular and Cellular Biology, May 2006, p. 3798-3809, Vol. 26, No. 10
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.10.3798-3809.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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