Oswald Evelyn, Reinz Eileen, Voit Renate, Aubin François, Alonso Angel, Auvinen Eeva
Research Program in Infection and Cancer, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Department of Dermatology, Université de Franche-Comté, Besançon, France.
Virus Genes. 2017 Dec;53(6):807-813. doi: 10.1007/s11262-017-1491-6. Epub 2017 Jul 21.
Our aim was to search for new cellular binding partners for the E6 and E7 oncogenes of beta human papillomaviruses (HPV), whose direct role in skin carcinogenesis has not been thoroughly investigated. By employing glutathione S-transferase pulldown and coimmunoprecipitation, we identified nuclear myosin 1c as a binding partner of HPV 8 E7 protein. As nuclear myosin 1c is an essential component of the RNA polymerase I transcription complex, we studied the effects of HPV 8 E7 protein expression on ribosomal RNA (rRNA) expression. Here we show that the activity of RNA polymerase I is decreased and that pre-rRNA expression is consequently reduced due to HPV 8 E7 expression. However, the expression levels of mature cytoplasmic 18S and 28S rRNA are retained. We propose that by relieving their resources from the energy-consuming process of rRNA transcription, HPV 8 E7 expressing cells might support more efficient virus replication in the differentiating epithelium.
我们的目标是寻找β型人乳头瘤病毒（HPV）E6和E7癌基因新的细胞结合伴侣，其在皮肤癌发生中的直接作用尚未得到充分研究。通过谷胱甘肽S-转移酶下拉实验和免疫共沉淀，我们鉴定出核肌球蛋白1c是HPV 8 E7蛋白的结合伴侣。由于核肌球蛋白1c是RNA聚合酶I转录复合体的重要组成部分，我们研究了HPV 8 E7蛋白表达对核糖体RNA（rRNA）表达的影响。在此我们表明，由于HPV 8 E7的表达，RNA聚合酶I的活性降低，前体rRNA表达因此减少。然而，成熟的细胞质18S和28S rRNA的表达水平得以保留。我们提出，通过将资源从rRNA转录的耗能过程中释放出来，表达HPV 8 E7的细胞可能在分化上皮细胞中支持更高效的病毒复制。
