Stabilization of HPV16 E6 protein by PDZ proteins, and potential implications for genome maintenance

Lietta Nicolaides, Clare Davy, Kenneth Raj, Christian Kranjec, Lawrence Banks, John Doorbar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

The E6 protein from high-risk human papillomaviruses appears necessary for persistence of viral episomes in cells but the underlying mechanism is unclear. E6 has many activities, including its ability to bind and degrade PDZ domain-containing proteins, such as hScrib. However little is known about the role of these interactions for E6 function and the viral life cycle. We now show that the levels of expression of wild-type E6 are increased in the presence of hScrib whilst a mutant E6 protein lacking the PDZ-binding motif is found at lower levels as it is turned over more rapidly by the proteasome. This correlates with an inability of genomes containing this mutation to be maintained as episomes. These results show that E6 association with certain PDZ domain-containing proteins can stabilize the levels of E6 expression and provides one explanation as to how the PDZ-binding capacity of E6 might contribute to genome episomal maintenance.

Original languageEnglish
Pages (from-to)137-145
Number of pages9
JournalVirology
Volume414
Issue number2
DOIs
Publication statusPublished - 5 Jun 2011

Bibliographical note

Funding Information:
This work was funded by the United Kingdom Medical Research Council grants U117584278 to J.D. and U117573807 to K.R., and by the Associazione Italiana per la Ricerca sul Cancro .

Keywords

  • E6
  • Genome maintenance
  • HPV
  • PDZ
  • Stability

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