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Originally published In Press as doi:10.1074/jbc.M208338200 on September 16, 2002

J. Biol. Chem., Vol. 277, Issue 47, 45347-45355, November 22, 2002
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Pescadillo Is Essential for Nucleolar Assembly, Ribosome Biogenesis, and Mammalian Cell Proliferation*

Alexandra Lerch-GagglDagger §, Jamil HaqueDagger §, Jixuan LiDagger , Gang NingDagger , Paula Traktman, and Stephen A. DuncanDagger ||

From the Dagger  Department of Cell Biology, Neurobiology, and Anatomy and the  Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Mutation of the zebrafish pescadillo gene blocks expansion of a number of tissues in the developing embryo, suggesting roles for its gene product in controlling cell proliferation. We report that levels of the pescadillo protein increase in rodent hepatocytes as they enter the cell cycle. Pescadillo protein localizes to distinct substructures of the interphase nucleus including nucleoli, the site of ribosome biogenesis. During mitosis pescadillo closely associates with the periphery of metaphase chromosomes and by late anaphase is associated with nucleolus-derived foci and prenucleolar bodies. Blastomeres in mouse embryos lacking pescadillo arrest at morula stages of development, the nucleoli fail to differentiate and accumulation of ribosomes is inhibited. We propose that in mammalian cells pescadillo is essential for ribosome biogenesis and nucleologenesis and that disruption to its function results in cell cycle arrest.

* This work was supported by Grants DK60064 and DK55743 from the NIDDK, National Institutes of Health (to S. A. D.) and grants from the Medical College of Wisconsin Digestive Disease Center.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ These authors contributed equally to this work.

|| To whom correspondence should be addressed. Tel.: 414-456-8602; Fax: 414-456-6517; E-mail: duncans@mcw.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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