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 Xu, Z.-X.
Right arrow Articles by Chang, K.-S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xu, Z.-X.
Right arrow Articles by Chang, K.-S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2003, p. 4247-4256, Vol. 23, No. 12
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.12.4247-4256.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

PML Colocalizes with and Stabilizes the DNA Damage Response Protein TopBP1

Zhi-Xiang Xu, Anna Timanova-Atanasova, Rui-Xun Zhao, and Kun-Sang Chang*

Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Received 18 November 2002/ Returned for modification 26 January 2003/ Accepted 25 March 2003

The PML tumor suppressor gene is consistently disrupted by t(15;17) in patients with acute promyelocytic leukemia. Promyelocytic leukemia protein (PML) is a multifunctional protein that plays essential roles in cell growth regulation, apoptosis, transcriptional regulation, and genome stability. Our study here shows that PML colocalizes and associates in vivo with the DNA damage response protein TopBP1 in response to ionizing radiation (IR). Both PML and TopBP1 colocalized with the IR-induced bromodeoxyuridine single-stranded DNA foci. PML and TopBP1 also colocalized with Rad50, Brca1, ATM, Rad9, and BLM. IR and interferon (IFN) coinduce the expression levels of both TopBP1 and PML. In PML-deficient NB4 cells, TopBP1 was unable to form IR-induced foci. All-trans-retinoic acid induced reorganization of the PML nuclear body (NB) and reappearance of the IR-induced TopBP1 foci. Inhibition of PML expression by siRNA is associated with a significant decreased in TopBP1 expression. Furthermore, PML-deficient cells express a low level of TopBP1, and its expression cannot be induced by IR or IFN. Adenovirus-mediated overexpression of PML in PML-/- mouse embryo fibroblasts substantially increased TopBP1 expression, which colocalized with the PML NBs. These studies demonstrated a mechanism of PML-dependent expression of TopBP1. PML overexpression induced TopBP1 protein but not the mRNA expression. Pulse-chase labeling analysis demonstrated that PML overexpression stabilized the TopBP1 protein, suggesting that PML plays a role in regulating the stability of TopBP1 in response to IR. Together, our findings demonstrate that PML regulates TopBP1 functions by association and stabilization of the protein in response to IR-induced DNA damage.

* Corresponding author. Mailing address: Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 89, Houston, TX 77030. Phone: (713) 792-2581. Fax: (713) 794-4672. E-mail: kchang{at}mail.mdanderson.org.

Molecular and Cellular Biology, June 2003, p. 4247-4256, Vol. 23, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.12.4247-4256.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ullman, A. J., Hearing, P. (2008). Cellular Proteins PML and Daxx Mediate an Innate Antiviral Defense Antagonized by the Adenovirus E4 ORF3 Protein. J. Virol. 82: 7325-7335 [Abstract] [Full Text]  
  • Cao, X., Clavijo, C., Li, X., Lin, H. H., Chen, Y., Shih, H.-M., Ann, D. K. (2008). SUMOylation of HMGA2: selective destabilization of promyelocytic leukemia protein via proteasome. Molecular Cancer Therapeutics 7: 923-934 [Abstract] [Full Text]  
  • Henderson, M. J., Munoz, M. A., Saunders, D. N., Clancy, J. L., Russell, A. J., Williams, B., Pappin, D., Khanna, K. K., Jackson, S. P., Sutherland, R. L., Watts, C. K. W. (2006). EDD Mediates DNA Damage-induced Activation of CHK2. J. Biol. Chem. 281: 39990-40000 [Abstract] [Full Text]  
  • Dellaire, G., Ching, R. W., Ahmed, K., Jalali, F., Tse, K. C.K., Bristow, R. G., Bazett-Jones, D. P. (2006). Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR. JCB 175: 55-66 [Abstract] [Full Text]  
  • Boe, S. O., Haave, M., Jul-Larsen, A., Grudic, A., Bjerkvig, R., Lonning, P. E. (2006). Promyelocytic leukemia nuclear bodies are predetermined processing sites for damaged DNA. J. Cell Sci. 119: 3284-3295 [Abstract] [Full Text]  
  • Luciani, J. J., Depetris, D., Usson, Y., Metzler-Guillemain, C., Mignon-Ravix, C., Mitchell, M. J., Megarbane, A., Sarda, P., Sirma, H., Moncla, A., Feunteun, J., Mattei, M.-G. (2006). PML nuclear bodies are highly organised DNA-protein structures with a function in heterochromatin remodelling at the G2 phase. J. Cell Sci. 119: 2518-2531 [Abstract] [Full Text]  
  • Schlegel, B. P., Jodelka, F. M., Nunez, R. (2006). BRCA1 Promotes Induction of ssDNA by Ionizing Radiation.. Cancer Res. 66: 5181-5189 [Abstract] [Full Text]  
  • Rao, V. A., Fan, A. M., Meng, L., Doe, C. F., North, P. S., Hickson, I. D., Pommier, Y. (2005). Phosphorylation of BLM, Dissociation from Topoisomerase III{alpha}, and Colocalization with {gamma}-H2AX after Topoisomerase I-Induced Replication Damage. Mol. Cell. Biol. 25: 8925-8937 [Abstract] [Full Text]  
  • Stracker, T. H., Lee, D. V., Carson, C. T., Araujo, F. D., Ornelles, D. A., Weitzman, M. D. (2005). Serotype-Specific Reorganization of the Mre11 Complex by Adenoviral E4orf3 Proteins. J. Virol. 79: 6664-6673 [Abstract] [Full Text]  
  • Evans, J. D., Hearing, P. (2005). Relocalization of the Mre11-Rad50-Nbs1 Complex by the Adenovirus E4 ORF3 Protein Is Required for Viral Replication. J. Virol. 79: 6207-6215 [Abstract] [Full Text]  
  • Everett, R. D., Murray, J. (2005). ND10 Components Relocate to Sites Associated with Herpes Simplex Virus Type 1 Nucleoprotein Complexes during Virus Infection. J. Virol. 79: 5078-5089 [Abstract] [Full Text]  
  • Takahashi, H., Hatakeyama, S., Saitoh, H., Nakayama, K. I. (2005). Noncovalent SUMO-1 Binding Activity of Thymine DNA Glycosylase (TDG) Is Required for Its SUMO-1 Modification and Colocalization with the Promyelocytic Leukemia Protein. J. Biol. Chem. 280: 5611-5621 [Abstract] [Full Text]  
  • Smilenov, L. B., Lieberman, H. B., Mitchell, S. A., Baker, R. A., Hopkins, K. M., Hall, E. J. (2005). Combined Haploinsufficiency for ATM and RAD9 as a Factor in Cell Transformation, Apoptosis, and DNA Lesion Repair Dynamics. Cancer Res. 65: 933-938 [Abstract] [Full Text]  
  • Licht, J. D., Sternberg, D. W. (2005). The Molecular Pathology of Acute Myeloid Leukemia. ASH Education Book 2005: 137-142 [Abstract] [Full Text]  
  • Bernassola, F., Salomoni, P., Oberst, A., Di Como, C. J., Pagano, M., Melino, G., Pandolfi, P. P. (2004). Ubiquitin-dependent Degradation of p73 Is Inhibited by PML. JEM 199: 1545-1557 [Abstract] [Full Text]  
  • Wilkinson, D. E., Weller, S. K. (2004). Recruitment of Cellular Recombination and Repair Proteins to Sites of Herpes Simplex Virus Type 1 DNA Replication Is Dependent on the Composition of Viral Proteins within Prereplicative Sites and Correlates with the Induction of the DNA Damage Response. J. Virol. 78: 4783-4796 [Abstract] [Full Text]  
  • Xu, Z.-X., Zhao, R.-X., Ding, T., Tran, T. T., Zhang, W., Pandolfi, P. P., Chang, K.-S. (2004). Promyelocytic Leukemia Protein 4 Induces Apoptosis by Inhibition of Survivin Expression. J. Biol. Chem. 279: 1838-1844 [Abstract] [Full Text]  
  • Yang, J., Yu, Y., Hamrick, H. E., Duerksen-Hughes, P. J. (2003). ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses. Carcinogenesis 24: 1571-1580 [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»