 |  |
| ||||
Copyright © 2008 Ainsworth et al; licensee BioMed Central Ltd. Comparison of p53 and the PDZ domain containing protein MAGI-3 regulation by the E6 protein from high-risk human papillomaviruses Julia Ainsworth,1 Miranda Thomas,2 Lawrence Banks,2 Francois Coutlee,3 and Greg Matlashewski  1,41Department of Microbiology and Immunology, McGill University, Montreal, QC., Canada 2International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste I-34012, Italy 3Department de Microbiologie et Immunologie, University de Montreal, QC., Canada 4Department of Microbiology and Immunology, McGill University, Montreal, H3A 2B4, 514-398-3914, Canada Corresponding author.Julia Ainsworth: j.ainsworth22/at/gmail.com; Miranda Thomas: Thomas/at/icgeb.org; Lawrence Banks: banks/at/icgeb.org; Francois Coutlee: francois.coutlee.chum/at/ssss.gouv.qc.ca; Greg Matlashewski: greg.matlashewski/at/mcgill.ca Received April 22, 2008; Accepted June 2, 2008. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | ||||
Abstract Central to cellular transformation caused by human papillomaviruses (HPVs) is the ability of E6 proteins to target cellular p53 and proteins containing PDZ domains, including MAGI-3, for degradation. The aim of this study was to compare E6-mediated degradation of p53 and MAGI-3 under parallel experimental conditions and further with respect to the involvement of proteasomes and ubiquitination. We also compared the degradation of p53 and MAGI-3 by E6 from several HPV types including different variants from HPV-33. All of the E6 genes from different HPV types displayed similar abilities to mediate the degradation of both p53 and MAGI-3 although there may be subtle differences observed with the different 33E6 variants. There were however differences in E6 mediated degradation of p53 and MAGI-3. Proteasome inhibition assays partially protected p53 from E6 mediated degradation, but did not protect MAGI-3. In addition, under conditions where p53 was ubiquitinated by E6 and MDM2 in vivo, ubiquitination of MAGI-3 was not detected. These results imply that although both p53 and MAGI-3 represent effective targets for oncogenic E6, the mechanisms by which E6 mediates p53 and MAGI-3 degradation are distinct with respect to the involvement of ubiquitination prior to proteasomal degradation. | ||||
