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Journal of Virology, June 2009, p. 5329-5338, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00089-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Identification of Integrin {alpha}3 as a New Substrate of the Adenovirus E4orf6/E1B 55-Kilodalton E3 Ubiquitin Ligase Complex{triangledown}

Frédéric Dallaire,1 Paola Blanchette,1 Peter Groitl,4 Thomas Dobner,4 and Philip E. Branton1,2,3*

Departments of Biochemistry,1 Oncology,2 Goodman Cancer Center, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada,3 Heinrich-Pette-Institute for Experimental Virology and Immunology, Martinistr. 52, 20251 Hamburg, Germany4

Received 14 January 2009/ Accepted 12 March 2009

The human adenovirus E4orf6 and E1B55K proteins promote viral replication by targeting several cellular proteins for degradation. The E4orf6 product has been shown by our group and others to form an E3 ubiquitin ligase complex that contains elongins B and C and cullin family member Cul5. E1B55K associates with this complex, where it is believed to function primarily to introduce bound substrates for degradation via proteasomes. In addition to p53, its first known substrate, the E4orf6/E1B 55-kDa complex (E4orf6/E1B55K) was shown to promote the degradation of Mre11 and DNA ligase IV; however, additional substrates are believed to exist. This notion is strengthened by the fact that none of these substrates seems likely to be associated with additional functions shown to be mediated by the E4orf6-associated E3 ubiquitin ligase complex, including export of late viral mRNAs and blockage of export of the bulk cellular mRNAs from the nucleus. In an attempt to identify new E4orf6/E1B55K substrates, we undertook a proteomic screen using human p53-null, non-small-cell lung carcinoma H1299 cells expressing either E4orf6 protein alone or in combination with E1B55K through infection by appropriate adenovirus vectors. One cellular protein that appeared to be degraded by E1B55K in combination with the E4orf6 protein was a species of molecular mass ~130 kDa that was identified as the integrin {alpha}3 subunit (i.e., very late activation antigen 3 alpha subunit). Preliminary analyses suggested that degradation of {alpha}3 may play a role in promoting release and spread of progeny virions.

* Corresponding author. Mailing address: Department of Biochemistry, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada. Phone: (514) 398-7268. Fax: (514) 398-7384. E-mail: philip.branton{at}mcgill.ca

{triangledown} Published ahead of print on 18 March 2009.

Journal of Virology, June 2009, p. 5329-5338, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00089-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dallaire, F., Blanchette, P., Branton, P. E. (2009). A Proteomic Approach To Identify Candidate Substrates of Human Adenovirus E4orf6-E1B55K and Other Viral Cullin-Based E3 Ubiquitin Ligases. J. Virol. 83: 12172-12184 [Abstract] [Full Text]  
  • Spurgeon, M. E., Ornelles, D. A. (2009). The Adenovirus E1B 55-Kilodalton and E4 Open Reading Frame 6 Proteins Limit Phosphorylation of eIF2{alpha} during the Late Phase of Infection. J. Virol. 83: 9970-9982 [Abstract] [Full Text]  
  • Kindsmuller, K., Schreiner, S., Leinenkugel, F., Groitl, P., Kremmer, E., Dobner, T. (2009). A 49-Kilodalton Isoform of the Adenovirus Type 5 Early Region 1B 55-Kilodalton Protein Is Sufficient To Support Virus Replication. J. Virol. 83: 9045-9056 [Abstract] [Full Text]  


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