Human Papillomavirus E6 interaction with cellular PDZ domain proteins modulates YAP nuclear localization.
Human Papillomavirus E6 interaction with cellular PDZ domain proteins modulates YAP nuclear localization.
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DOI：
10.1016/j.virol.2018.01.003
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发表时间：
2018-03
期刊：
影响因子：
3.7
通讯作者：
Vande Pol SB
中科院分区：
文献类型：
--
作者：
Webb Strickland S;Brimer N;Lyons C;Vande Pol SB
HPV E6癌蛋白与细胞PDZ蛋白相关。除了先前鉴定的细胞PDZ蛋白外，我们还发现HPV 16 E6 PBM与肌营养不良蛋白糖蛋白复合物、LRCC 1和SLC 9A 3R 2相关。当使用来自腺瘤细胞系的裂解物时，HPV 18 E6具有额外的关联，包括LRPPRC、RLGAPB、EIF 3A、SMC 2和3、AMOT、AMOTL 1和ARHGEF 1;这些细胞PDZ蛋白中的一些涉及YAP 1转录辅激活因子的调节。在角质形成细胞中，完整的HPV-16基因组或E6或E7癌蛋白的表达促进了YAP 1的核转位; E6的活性需要羧基末端的完整PBM。这项工作表明E6与细胞PDZ蛋白的结合促进了YAP 1的核定位。因此，E6促进雅普核转运的能力鉴定了可能有助于E6转化细胞的E6活性。
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 YAP thus identifies an E6 activity that could contribute to the transformation of cells by E6.
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