Muench Peter, Hiller Thomas, Probst Sonja, Florea Ana-Maria, Stubenrauch Frank, Iftner Thomas
Universitaetsklinikum Tuebingen, Germany.
Virology. 2009 May 10;387(2):380-7. doi: 10.1016/j.virol.2009.02.018. Epub 2009 Mar 14.
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.
有确凿证据表明高危型人乳头瘤病毒（HPV）可引发宫颈癌。引人注目的是，HPV16和18约占所有宫颈癌的70%，而在系统发育上相关的其他类型出现频率则低得多。很可能，病毒E6和E7癌蛋白活性的差异导致了体内致癌性。我们在此证明，低危型HPV70的E6蛋白以及可能的高危型HPV82的E6蛋白与PDZ蛋白hDlg和Magi1相互作用并使其降解，这与HPV16 E6和HPV18 E6相同。相比之下，高危型HPV66 E6不结合或降解hDlg或Magi1。我们还表明，低危型HPV70 E6/E7可使正常人角质形成细胞永生化。结合我们之前关于p53降解的分析，这表明E6与p53、E6AP、Magi1和hDlg的结合、hDlg和Magi1的降解，以及正常人角质形成细胞的永生化，似乎都不是HPV在宫颈致癌行为的可靠预测指标。
