HPV E6 oncoproteins associate with cellular PDZ proteins. In addition to previously identified cellular PDZ proteins, we found association of the HPV16 E6 PBM with the Dystrophin Glycoprotein Complex, LRCC1, and SLC9A3R2. HPV18 E6 had additional associations when lysates from adenomatous cell lines were used including LRPPRC, RLGAPB, EIF3A, SMC2 and 3, AMOT, AMOTL1, and ARHGEF1; some of these cellular PDZ proteins are implicated in the regulation of the YAP1 transcriptional co-activator. In keratinocytes, nuclear translocation of YAP1 was promoted by the complete HPV-16 genome, or by expression of the individual E6 or E7 oncoproteins; the activity of E6 required an intact PBM at the carboxy-terminus. This work demonstrates that E6 association with cellular PDZ proteins promotes the nuclear localization of YAP1. The ability of E6 to promote the nuclear transport of YAP1 thus identifies an E6 activity that could contribute to the transformation of cells by E6.

HPV E6癌蛋白与细胞PDZ蛋白相关。除了先前确定的细胞PDZ蛋白外，我们还发现HPV16 E6 PBM与肌营养不良蛋白糖蛋白复合物，LRCC1和SLC9A3R2相关。当使用来自腺瘤细胞系的裂解物时，HPV18 E6具有其他关联，包括LRPPRC，RLGAPB，EIF3A，SMC2和3，AMOT，AMOTL1和ARHGEF1。这些细胞PDZ蛋白中有一些与YAP1转录共激活因子的调控有关。在角质形成细胞中，完整的HPV-16基因组或单个E6或E7癌蛋白的表达促进了YAP1的核易位。E6的活性需要在羧基末端有完整的PBM。这项工作表明，E6与细胞PDZ蛋白的结合会促进YAP1的核定位。