title: Stabilization of HPV16 E6 protein by PDZ proteins, and potential implications for genome maintenance.
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.
authors.affiliation: Division of Virology, MRC National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Lietta
authors.initials: L
authors.lastname: Nicolaides
authors.forename: Clare
authors.initials: C
authors.lastname: Davy
authors.forename: Kenneth
authors.initials: K
authors.lastname: Raj
authors.forename: Christian
authors.initials: C
authors.lastname: Kranjec
authors.forename: Lawrence
authors.initials: L
authors.lastname: Banks
authors.forename: John
authors.initials: J
authors.lastname: Doorbar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D000074288:Discs Large Homolog 1 Protein; D016679:Genome, Viral; D051528:Guanylate Kinases; D052162:Human papillomavirus 16 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054731:PDZ Domains; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000821:virology; D011485:Protein Binding; D055550:Protein Stability; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; C068651:E6 protein, Human papillomavirus type 16; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins; D051528:Guanylate Kinases; C113338:MAGI1 protein, human