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Published online
doi:10.1083/jcb.200807185
The Journal of Cell Biology, Vol. 183, No. 4, 589-595
The Rockefeller University Press, 0021-9525 $30.00
© Yun et al.
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Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases



Chawon Yun1, Yonggang Wang1, Debaditya Mukhopadhyay1, Peter Backlund2, Nagamalleswari Kolli3, Alfred Yergey2, Keith D. Wilkinson3, and Mary Dasso1

1 Laboratory of Gene Regulation and Development, 2 Section on Mass Spectrometry & Metabolism/Office of the Scientific Director, National Institute of Child Health and Human Development, Bethesda, MD 20892
3 Department of Biochemistry, Emory University, Atlanta, GA 30322

Correspondence to Mary Dasso: mdasso{at}helix.nih.gov

Ubiquitin-like protein/sentrin-specific proteases (Ulp/SENPs) mediate both processing and deconjugation of small ubiquitin-like modifier proteins (SUMOs). Here, we show that Ulp/SENP family members SENP3 and SENP5 localize within the granular component of the nucleolus, a subnucleolar compartment that contains B23/nucleophosmin. B23/nucleophosmin is an abundant shuttling phosphoprotein, which plays important roles in ribosome biogenesis and which has been strongly implicated in hematopoietic malignancies. Moreover, we found that B23/nucleophosmin binds SENP3 and SENP5 in Xenopus laevis egg extracts and that it is essential for stable accumulation of SENP3 and SENP5 in mammalian tissue culture cells. After either codepletion of SENP3 and SENP5 or depletion of B23/nucleophosmin, we observed accumulation of SUMO proteins within nucleoli. Finally, depletion of these Ulp/SENPs causes defects in ribosome biogenesis reminiscent of phenotypes observed in the absence of B23/nucleophosmin. Together, these results suggest that regulation of SUMO deconjugation may be a major facet of B23/nucleophosmin function in vivo.

C. Yun and Y. Wang contributed equally to this paper.

C. Yun's present address is Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.

Abbreviations used in this paper: Ni-NTA, nickel–nitrilotriacetic acid; RNAi, RNA interference; rRNA, ribosomal RNA; SUMO, small ubiquitin-like modifier protein; Ulp/SENP, ubiquitin-like protein/sentrin-specific protease; XEE, Xenopus laevis egg extract; xSENP3, Xenopus SENP3.

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