This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vogt Sionov, R.
Right arrow Articles by Haupt, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vogt Sionov, R.
Right arrow Articles by Haupt, Y.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2001, p. 5869-5878, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.5869-5878.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

c-Abl Regulates p53 Levels under Normal and Stress Conditions by Preventing Its Nuclear Export and Ubiquitination

Ronit Vogt Sionov,1 Sabrina Coen,1 Zehavit Goldberg,1 Michael Berger,1 Beatrice Bercovich,2 Yinon Ben-Neriah,1 Aaron Ciechanover,2 and Ygal Haupt1,*

Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120,1 and Department of Biochemistry, The Rappaport Family Institute for Research in the Medical Sciences and the Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096,2 Israel

Received 8 March 2001/Returned for modification 11 May 2001/Accepted 4 June 2001

The p53 protein is subject to Mdm2-mediated degradation by the ubiquitin-proteasome pathway. This degradation requires interaction between p53 and Mdm2 and the subsequent ubiquitination and nuclear export of p53. Exposure of cells to DNA damage results in the stabilization of the p53 protein in the nucleus. However, the underlying mechanism of this effect is poorly defined. Here we demonstrate a key role for c-Abl in the nuclear accumulation of endogenous p53 in cells exposed to DNA damage. This effect of c-Abl is achieved by preventing the ubiquitination and nuclear export of p53 by Mdm2, or by human papillomavirus E6. c-Abl null cells fail to accumulate p53 efficiently following DNA damage. Reconstitution of these cells with physiological levels of c-Abl is sufficient to promote the normal response of p53 to DNA damage via nuclear retention. Our results help to explain how p53 is accumulated in the nucleus in response to DNA damage.

* Corresponding author. Mailing address: Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel. Phone: 972-2-6757103. Fax: 972-2-6424653. E-mail: haupt{at}md.huji.ac.il.

Molecular and Cellular Biology, September 2001, p. 5869-5878, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.5869-5878.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Zuckerman, V., Lenos, K., Popowicz, G. M., Silberman, I., Grossman, T., Marine, J.-C., Holak, T. A., Jochemsen, A. G., Haupt, Y. (2009). c-Abl Phosphorylates Hdmx and Regulates Its Interaction with p53. J. Biol. Chem. 284: 4031-4039 [Abstract] [Full Text]  
  • Alshatwi, A. A., Han, C.-T., Schoene, N. W., Lei, K. Y. (2006). Nuclear Accumulations of p53 and Mdm2 Are Accompanied by Reductions in c-Abl and p300 in Zinc-Depleted Human Hepatoblastoma Cells.. Exp. Biol. Med. 231: 611-618 [Abstract] [Full Text]  
  • Zeng, L., Hu, Y., Li, B. (2005). Identification of TopBP1 as a c-Abl-interacting Protein and a Repressor for c-Abl Expression. J. Biol. Chem. 280: 29374-29380 [Abstract] [Full Text]  
  • Wei, G., Li, A. G., Liu, X. (2005). Insights into Selective Activation of p53 DNA Binding by c-Abl. J. Biol. Chem. 280: 12271-12278 [Abstract] [Full Text]  
  • Gaughan, L., Logan, I. R., Neal, D. E., Robson, C. N. (2005). Regulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation. Nucleic Acids Res 33: 13-26 [Abstract] [Full Text]  
  • Kim, H., Kwak, N.-J., Lee, J. Y., Choi, B. H., Lim, Y., Ko, Y. J., Kim, Y.-H., Huh, P.-W., Lee, K.-H., Rha, H. K., Wang, Y.-P. (2004). Merlin Neutralizes the Inhibitory Effect of Mdm2 on p53. J. Biol. Chem. 279: 7812-7818 [Abstract] [Full Text]  
  • Iwakuma, T., Lozano, G. (2003). MDM2, An Introduction. Mol Cancer Res 1: 993-1000 [Abstract] [Full Text]  
  • Meek, D. W., Knippschild, U. (2003). Posttranslational Modification of MDM2. Mol Cancer Res 1: 1017-1026 [Abstract] [Full Text]  
  • Louria-Hayon, I., Grossman, T., Sionov, R. V., Alsheich, O., Pandolfi, P. P., Haupt, Y. (2003). The Promyelocytic Leukemia Protein Protects p53 from Mdm2-mediated Inhibition and Degradation. J. Biol. Chem. 278: 33134-33141 [Abstract] [Full Text]  
  • Prisco, M., Santini, F., Baffa, R., Liu, M., Drakas, R., Wu, A., Baserga, R. (2002). Nuclear Translocation of Insulin Receptor Substrate-1 by the Simian Virus 40 T Antigen and the Activated Type 1 Insulin-like Growth Factor Receptor. J. Biol. Chem. 277: 32078-32085 [Abstract] [Full Text]  
  • Raina, D., Mishra, N., Kumar, S., Kharbanda, S., Saxena, S., Kufe, D. (2002). Inhibition of c-Abl with STI571 Attenuates Stress-Activated Protein Kinase Activation and Apoptosis in the Cellular Response to 1-beta -D-Arabinofuranosylcytosine. Mol. Pharmacol. 61: 1489-1495 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»