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 Jiang, P.
Right arrow Articles by Wu, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jiang, P.
Right arrow Articles by Wu, M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2006, p. 9071-9082, Vol. 26, No. 23
0270-7306/06/$08.00+0     doi:10.1128/MCB.01025-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Bad Guy Cooperates with Good Cop p53: Bad Is Transcriptionally Up-Regulated by p53 and Forms a Bad/p53 Complex at the Mitochondria To Induce Apoptosis{triangledown}

Peng Jiang,1,{dagger} Wenjing Du,1,{dagger} Klaus Heese,2 and Mian Wu1*

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China,1 Department of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore2

Received 8 June 2006/ Returned for modification 7 July 2006/ Accepted 8 September 2006

Although the regulation of several Bcl-2 family molecules, including Puma, Noxa, Bax, and Bid, by p53 has been studied intensively, the interplay between Bad (Bcl-2 antagonist of cell death) and p53 has not yet been reported thus far. Here, we report that p53 activates Bad transcription and expression through binding to a short conserved sequence located approximately 6.6 kb upstream of the translation start point. We also demonstrate that Bad physically interacts with cytoplasmic p53, thereby preventing p53 from entering the nucleus and resulting in reduced transcription of Bad. Moreover, Bad is able to direct p53 to the mitochondria and forms a p53/Bad complex at the mitochondria. Two lines of evidences support this hypothesis: first, when mitochondria purified from p53-deficient H1299 cells are incubated with p53 and either wild-type (wt) Bad or mutant Bad (this mutant binds p53 yet is unable to migrate to mitochondria), p53 can be detected only in mitochondria incubated with wt Bad and not in those incubated with mutant Bad; second, knockdown of Bad expression reduces mitochondrial localization of p53. The mitochondrial p53/Bad complex promotes apoptosis via activation and oligomerization of Bak. Elimination of Bad expression by RNA interference notably attenuates apoptosis induced by etoposide. Hence, our collective data provide the first evidence that Bad plays dual roles in both p53 transcription-dependent and -independent pathways.

* Corresponding author. Mailing address: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China. Phone: 86-551-3607324. Fax: 86-551-3606264. E-mail: wumian{at}ustc.edu.cn.

{triangledown} Published ahead of print on 25 September 2006.

{dagger} These authors contributed equally to this work.

Molecular and Cellular Biology, December 2006, p. 9071-9082, Vol. 26, No. 23
0270-7306/06/$08.00+0     doi:10.1128/MCB.01025-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • McDonough, H., Charles, P. C., Hilliard, E. G., Qian, S.-b., Min, J.-N., Portbury, A., Cyr, D. M., Patterson, C. (2009). Stress-dependent Daxx-CHIP Interaction Suppresses the p53 Apoptotic Program. J. Biol. Chem. 284: 20649-20659 [Abstract] [Full Text]  
  • Ortiz, R. J., Lizama, C., Codelia, V. A., Moreno, R. D. (2009). A molecular evaluation of germ cell death induced by etoposide in pubertal rat testes. Mol Hum Reprod 15: 363-371 [Abstract] [Full Text]  
  • Pietsch, E. C., Perchiniak, E., Canutescu, A. A., Wang, G., Dunbrack, R. L., Murphy, M. E. (2008). Oligomerization of BAK by p53 Utilizes Conserved Residues of the p53 DNA Binding Domain. J. Biol. Chem. 283: 21294-21304 [Abstract] [Full Text]  
  • Guicciardi, M. E., Gores, G. J. (2008). Cell Stress Gives a Red Light to the Mitochondrial Cell Death Pathway. Sci Signal 1: pe9-pe9 [Abstract] [Full Text]  
  • Li, Y.-Z., Lu, D.-Y., Tan, W.-Q., Wang, J.-X., Li, P.-F. (2008). p53 Initiates Apoptosis by Transcriptionally Targeting the Antiapoptotic Protein ARC. Mol. Cell. Biol. 28: 564-574 [Abstract] [Full Text]  
  • Leu, J. I-J., George, D. L. (2007). Hepatic IGFBP1 is a prosurvival factor that binds to BAK, protects the liver from apoptosis, and antagonizes the proapoptotic actions of p53 at mitochondria. Genes Dev. 21: 3095-3109 [Abstract] [Full Text]  
  • Sot, B., Freund, S. M. V., Fersht, A. R. (2007). Comparative Biophysical Characterization of p53 with the Pro-apoptotic BAK and the Anti-apoptotic BCL-xL. J. Biol. Chem. 282: 29193-29200 [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»