Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

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.



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A cis-element with mixed G-quadruplex structure of NPGPx promoter is essential for nucleolin-mediated transactivation on non-targeting siRNA stress.
P.-C. Wei, Z.-F. Wang, W.-T. Lo, M.-I. Su, J.-Y. Shew, T.-C. Chang, and W.-H. Lee (2013)
Nucleic Acids Res. 41, 1533-1543
   Abstract »    Full Text »    PDF »
Nucleolin Protein Interacts with Microprocessor Complex to Affect Biogenesis of MicroRNAs 15a and 16.
B. F. Pickering, D. Yu, and M. W. Van Dyke (2011)
J. Biol. Chem. 286, 44095-44103
   Abstract »    Full Text »    PDF »
An ataxia-telangiectasia-mutated (ATM) kinase mediated response to DNA damage down-regulates the mRNA-binding potential of THOC5.
S. Ramachandran, D. D. H. Tran, S. Klebba-Faerber, C. Kardinal, A. D. Whetton, and T. Tamura (2011)
RNA 17, 1957-1966
   Abstract »    Full Text »    PDF »
Quantitative Proteomics and Dynamic Imaging of the Nucleolus Reveal Distinct Responses to UV and Ionizing Radiation.
H. M. Moore, B. Bai, F.-M. Boisvert, L. Latonen, V. Rantanen, J. C. Simpson, R. Pepperkok, A. I. Lamond, and M. Laiho (2011)
Mol. Cell. Proteomics 10, M111.009241
   Abstract »    Full Text »    PDF »
Targeting MYC Expression through G-Quadruplexes.
T. A. Brooks and L. H. Hurley (2010)
Genes & Cancer 1, 641-649
   Abstract »    Full Text »    PDF »
Anticancer Activity of CX-3543: A Direct Inhibitor of rRNA Biogenesis.
D. Drygin, A. Siddiqui-Jain, S. O'Brien, M. Schwaebe, A. Lin, J. Bliesath, C. B. Ho, C. Proffitt, K. Trent, J. P. Whitten, et al. (2009)
Cancer Res. 69, 7653-7661
   Abstract »    Full Text »    PDF »
p53 is localized to a sub-nucleolar compartment after proteasomal inhibition in an energy-dependent manner.
O. Karni-Schmidt, A. Zupnick, M. Castillo, A. Ahmed, T. Matos, P. Bouvet, C. Cordon-Cardo, and C. Prives (2008)
J. Cell Sci. 121, 4098-4105
   Abstract »    Full Text »    PDF »
The Nucleolus Exhibits an Osmotically Regulated Gatekeeping Activity That Controls the Spatial Dynamics and Functions of Nucleolin.
L. Yang, J. M. Reece, J. Cho, C. D. Bortner, and S. B. Shears (2008)
J. Biol. Chem. 283, 11823-11831
   Abstract »    Full Text »    PDF »
Nucleolin regulates c-Jun/Sp1-dependent transcriptional activation of cPLA2{alpha} in phorbol ester-treated non-small cell lung cancer A549 cells.
J.-H. Tsou, K.-Y. Chang, W.-C. Wang, J. T. Tseng, W.-C. Su, L.-Y. Hung, W.-C. Chang, and B.-K. Chen (2008)
Nucleic Acids Res. 36, 217-227
   Abstract »    Full Text »    PDF »
Depletion of the Nucleolar Protein Nucleostemin Causes G1 Cell Cycle Arrest via the p53 Pathway.
H. Ma and T. Pederson (2007)
Mol. Biol. Cell 18, 2630-2635
   Abstract »    Full Text »    PDF »
Nucleolin Regulates Gene Expression in CD34-positive Hematopoietic Cells.
E. Grinstein, Y. Du, S. Santourlidis, J. Christ, M. Uhrberg, and P. Wernet (2007)
J. Biol. Chem. 282, 12439-12449
   Abstract »    Full Text »    PDF »
Cell Cycle-controlled Interaction of Nucleolin with the Retinoblastoma Protein and Cancerous Cell Transformation.
E. Grinstein, Y. Shan, L. Karawajew, P. J. F. Snijders, C. J. L. M. Meijer, H.-D. Royer, and P. Wernet (2006)
J. Biol. Chem. 281, 22223-22235
   Abstract »    Full Text »    PDF »
Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths.
Y.-L. Wu, C. Dudognon, E. Nguyen, J. Hillion, F. Pendino, I. Tarkanyi, J. Aradi, M. Lanotte, J.-H. Tong, G.-Q. Chen, et al. (2006)
J. Cell Sci. 119, 2797-2806
   Abstract »    Full Text »    PDF »
A Chromatin-associated and Transcriptionally Inactive p53-Mdm2 Complex Occurs in mdm2 SNP309 Homozygous Cells.
N. C. Arva, T. R. Gopen, K. E. Talbott, L. E. Campbell, A. Chicas, D. E. White, G. L. Bond, A. J. Levine, and J. Bargonetti (2005)
J. Biol. Chem. 280, 26776-26787
   Abstract »    Full Text »    PDF »
The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesis.
C. Mayer, H. Bierhoff, and I. Grummt (2005)
Genes & Dev. 19, 933-941
   Abstract »    Full Text »    PDF »
Novel Checkpoint Response to Genotoxic Stress Mediated by Nucleolin-Replication Protein A Complex Formation.
K. Kim, D. D. Dimitrova, K. M. Carta, A. Saxena, M. Daras, and J. A. Borowiec (2005)
Mol. Cell. Biol. 25, 2463-2474
   Abstract »    Full Text »    PDF »
Nucleophosmin (B23) Targets ARF to Nucleoli and Inhibits Its Function.
C. Korgaonkar, J. Hagen, V. Tompkins, A. A. Frazier, C. Allamargot, F. W. Quelle, and D. E. Quelle (2005)
Mol. Cell. Biol. 25, 1258-1271
   Abstract »    Full Text »    PDF »
Aprataxin, a novel protein that protects against genotoxic stress.
N. Gueven, O. J. Becherel, A. W. Kijas, P. Chen, O. Howe, J. H. Rudolph, R. Gatti, H. Date, O. Onodera, G. Taucher-Scholz, et al. (2004)
Hum. Mol. Genet. 13, 1081-1093
   Abstract »    Full Text »    PDF »
S100C/A11 is a key mediator of Ca2+-induced growth inhibition of human epidermal keratinocytes.
M. Sakaguchi, M. Miyazaki, M. Takaishi, Y. Sakaguchi, E. Makino, N. Kataoka, H. Yamada, M. Namba, and N.-h. Huh (2003)
J. Cell Biol. 163, 825-835
   Abstract »    Full Text »    PDF »
Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage and other stresses.
C. P. Rubbi and J. Milner (2003)
EMBO J. 22, 6068-6077
   Abstract »    Full Text »    PDF »
Perturbations of chromatin structure in human genetic disease: recent advances.
W. A. Bickmore and S. M. van der Maarel (2003)
Hum. Mol. Genet. 12, R207-R213
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882