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
Google Scholar
Right arrow Articles by Pim, D.
Right arrow Articles by Banks, L.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pim, D.
Right arrow Articles by Banks, L.

 Previous Article  |  Next Article 

Journal of Virology, October 2009, p. 9863-9874, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00539-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Human Papillomavirus (HPV) E6* Proteins from High-Risk, Mucosal HPVs Can Direct Degradation of Cellular Proteins in the Absence of Full-Length E6 Protein{triangledown}

David Pim,* Vjekoslav Tomaic, and Lawrence Banks

International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34012 Trieste, Italy

Received 16 March 2009/ Accepted 16 July 2009

The E6 oncoproteins from high-risk mucosotrophic human papillomaviruses (HPVs) target a range of cellular proteins for proteasome-mediated degradation. Apart from the tumor suppressor p53 and proapoptotic Bcl-2 family member Bak, many targets contain class 1 PDZ domains and are involved in cell junction stability and signaling. The targeting mechanism is considered to function by the E6 protein acting as an adaptor molecule linking a cellular ubiquitin ligase to the target protein. In each case, whether the target is the p53 tumor suppressor or a member of the group of PDZ domain-containing targets, this mechanism relies on a direct interaction between E6 and its cellular target. This study focuses on the impact of the HPV type 18 (HPV-18) E6*I protein on the stability of Akt, Dlg, MAGI-1, MAGI-2, and Scribble. We show that HPV-18 E6* expression can downregulate the expression levels of Akt, Dlg, and Scribble in the absence of full-length HPV-18 E6 protein. The reduction in Dlg levels by E6* is independent of transcription and does not require a direct interaction between the two proteins although the proteasome pathway is involved. Further, we provide evidence that activation of certain signal transduction pathways has a profound effect on the targeting of Dlg by E6* and suggest that high-risk HPV E6 oncoproteins can target certain substrates both directly and indirectly through the E6* proteins and may cooperate in their degradation.

* Corresponding author. Mailing address: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34012 Trieste, Italy. Phone: 39 040 3757331. Fax: 39 040 226555. E-mail: pim{at}icgeb.org

{triangledown} Published ahead of print on 29 July 2009.

Journal of Virology, October 2009, p. 9863-9874, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00539-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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