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• W575897588 abstract "The E6 protein from high-risk Human Papillomaviruses (HPVs) has previouslybeen shown to be necessary for the persistence of viral episomes in cells,however, the mechanism for this remains unclear. High-risk E6 proteins havemany activities including the ability to degrade p53 and the ability to bind to anddegrade PDZ proteins. In this study I aimed to further elucidate the role of E6 inthe persistence of viral episomes.I used two HPV16 mutant genomes with mutations in the E6 open-readingframe; one that is unable to degrade p53 (16E6p53m), and one that lacks thePDZ-binding motif (16E6PDZ). I found that both are unable to persist episomallyin cells thereby implicating these two activities of E6 in HPV episomalpersistence.Upon closer investigation of the two mutant genomes, I found that the16E6p53m genome does not replicate as efficiently as the wild-type genome.This result suggests a function for p53-degradation in genome replication, andconsequently in genome persistence. Furthermore, by carrying out a moredetailed analysis of the relationship between E6 and the PDZ protein hScrib, Ishowed that the wild-type E6 protein is stabilised by virtue of the PDZ-bindingmotif, present on its C-terminus. On the other hand, the mutant E6 protein thatlacks the PDZ-binding motif (E6PDZ) is more susceptible to proteasomaldegradation. These findings provide evidence for a previously unknownoutcome of the E6-PDZ protein interaction, in stabilising wild-type E6 protein. Inaddition to the implications of this stabilisation in the persistence of viralepisomes, it is also significant when considering the activities and properties ofE6 that contribute to the development of neoplasia.Finally, I have also found that wild-type HPV16 genomes cannot persist in cellsthat constitutively express E6 protein, suggesting that the correct regulation ofE6 expression is crucial." @default.
• W575897588 created "2016-06-24" @default.
• W575897588 creator A5066816819 @default.
• W575897588 date "2011-10-28" @default.
• W575897588 modified "2023-09-28" @default.
• W575897588 title "Interactions of the human papillomavirus E6 protein and their role in the persistence of viral episomes" @default.
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