title: Binding of PDZ proteins to HPV E6 proteins does neither correlate with epidemiological risk classification nor with the immortalization of foreskin keratinocytes.
abstract: There is compelling evidence that high-risk human papillomaviruses (HPV) can cause cervical cancer. Strikingly, HPV16 and 18 account for approximately 70% of all cervical cancers, whereas phylogenetically related types are found at much lower frequencies. Most likely, differences in the activities of the viral E6 and E7 oncoproteins account for the in vivo carcinogenicity. We demonstrate here that E6 proteins from low-risk HPV70 and possibly high-risk HPV82 interact and degrade PDZ proteins hDlg and Magi1 identical to HPV16E6 and HPV18E6. In contrast high-risk HPV66E6 did not bind or degrade hDlg or Magi1. We also show that low-risk HPV70 E6/E7 immortalizes normal human keratinocytes. Together with our previous analysis concerning p53 degradation, this shows that neither binding of E6 to p53, to E6AP, to Magi1 and hDlg, the degradation of hDlg and Magi1, nor immortalization of normal human keratinocytes seems to be a reliable predictor for carcinogenic behavior of HPV in the cervix.
authors.affiliation: Universitaetsklinikum Tuebingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Muench
authors.forename: Thomas
authors.initials: T
authors.lastname: Hiller
authors.forename: Sonja
authors.initials: S
authors.lastname: Probst
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Florea
authors.forename: Frank
authors.initials: F
authors.lastname: Stubenrauch
authors.forename: Thomas
authors.initials: T
authors.lastname: Iftner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D000074288:Discs Large Homolog 1 Protein; D005260:Female; D052816:Foreskin / Q000166:cytology / Q000821:virology; D016147:Genes, Tumor Suppressor; D051528:Guanylate Kinases; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D054731:PDZ Domains; D027383:Papillomaviridae / Q000145:classification / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000150:complications*; D011485:Protein Binding; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000821:virology*
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; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D051528:Guanylate Kinases; C113338:MAGI1 protein, human