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Mol. Cell. Biol. 22 (16): 6014-6022

Copyright © 2002 by the American Society for Microbiology. All rights reserved.

Stress-Dependent Nucleolin Mobilization Mediated by p53-Nucleolin Complex Formation

Yaron Daniely,,{dagger} Diana D. Dimitrova, and James A. Borowiec*

Department of Biochemistry and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016

Received for publication 11 April 2002. Accepted for publication 8 May 2002.

Abstract: We recently discovered that heat shock causes nucleolin to relocalize from the nucleolus to the nucleoplasm, whereupon it binds replication protein A and inhibits DNA replication initiation. We report that nucleolin mobilization also occurs following exposure to ionizing radiation (IR) and treatment with camptothecin. Mobilization was selective in that another nucleolar marker, upstream binding factor, did not relocalize in response to IR. Nucleolin relocalization was dependent on p53 and stress, the latter initially stimulating nucleolin-p53 complex formation. Nucleolin relocalization and complex formation in vivo were independent of p53 transactivation but required the p53 C-terminal regulatory domain. Nucleolin and p53 also interact directly in vitro, with a similar requirement for p53 domains. These data indicate a novel p53-dependent mechanism in which cell stress mobilizes nucleolin for transient replication inhibition and DNA repair.

* Corresponding author. Mailing address: Department of Biochemistry, New York University School of Medicine, 550 First Ave., New York, NY 10016. Phone: (212) 263-8453. Fax: (212) 263-8166. E-mail: James.Borowiec{at}med.nyu.edu.

{dagger} Present address: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel 76100.

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