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 Schwartz, R. A.
Right arrow Articles by Weitzman, M. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schwartz, R. A.
Right arrow Articles by Weitzman, M. D.

 Previous Article  |  Next Article 

Journal of Virology, September 2008, p. 9043-9055, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00925-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Distinct Requirements of Adenovirus E1b55K Protein for Degradation of Cellular Substrates{triangledown}

Rachel A. Schwartz,1,2 Seema S. Lakdawala,1,2 Heather D. Eshleman,1,{dagger} Matthew R. Russell,1 Christian T. Carson,1,2,{ddagger} and Matthew D. Weitzman1*

Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037,1 Graduate Program, Division of Biology, University of California, San Diego, California 920932

Received 4 May 2008/ Accepted 3 July 2008

The E1b55K and E4orf6 proteins of adenovirus type 5 (Ad5) assemble into a complex together with cellular proteins including cullin 5, elongins B and C, and Rbx1. This complex possesses E3 ubiquitin ligase activity and targets cellular proteins for proteasome-mediated degradation. The ligase activity has been suggested to be responsible for all functions of E1b55K/E4orf6, including promoting efficient viral DNA replication, preventing a cellular DNA damage response, and stimulating late viral mRNA nuclear export and late protein synthesis. The known cellular substrates for degradation by E1b55K/E4orf6 are the Mre11/Rad50/Nbs1 DNA repair complex, the tumor suppressor p53, and DNA ligase IV. Here we show that the degradation of individual targets can occur independently of other substrates. Furthermore, we identify separation-of-function mutant forms of E1b55K that can distinguish substrates for binding and degradation. Our results identify distinct regions of E1b55K that are involved in substrate recognition but also imply that there are additional requirements beyond protein association. These mutant proteins will facilitate the determination of the relevance of specific substrates to the functions of E1b55K in promoting infection and inactivating host defenses.

* Corresponding author. Mailing address: Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 453-4100, ext. 2037. Fax: (858) 558-7454. E-mail: weitzman{at}salk.edu

{triangledown} Published ahead of print on 9 July 2008.

{dagger} Present address: Tetrad Graduate Program, University of California, San Francisco, CA.

{ddagger} Present address: Becton Dickinson Biosciences, San Diego, CA.

Journal of Virology, September 2008, p. 9043-9055, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00925-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dallaire, F., Blanchette, P., Groitl, P., Dobner, T., Branton, P. E. (2009). Identification of Integrin {alpha}3 as a New Substrate of the Adenovirus E4orf6/E1B 55-Kilodalton E3 Ubiquitin Ligase Complex. J. Virol. 83: 5329-5338 [Abstract] [Full Text]  
  • Blackford, A. N., Grand, R. J. A. (2009). Adenovirus E1B 55-Kilodalton Protein: Multiple Roles in Viral Infection and Cell Transformation. J. Virol. 83: 4000-4012 [Full Text]  
  • Thomas, M. A., Broughton, R. S., Goodrum, F. D., Ornelles, D. A. (2009). E4orf1 Limits the Oncolytic Potential of the E1B-55K Deletion Mutant Adenovirus. J. Virol. 83: 2406-2416 [Abstract] [Full Text]  
  • Nash, K., Chen, W., Salganik, M., Muzyczka, N. (2009). Identification of Cellular Proteins That Interact with the Adeno-Associated Virus Rep Protein. J. Virol. 83: 454-469 [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»