Tomaić Vjekoslav, Pim David, Banks Lawrence
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
Virology. 2009 Oct 10;393(1):7-10. doi: 10.1016/j.virol.2009.07.029. Epub 2009 Aug 22.
Human papillomavirus (HPV) E6 oncoproteins target numerous cellular proteins for ubiquitin-mediated degradation. In the case of p53 this is mediated by the E6AP ubiquitin ligase. However, there are conflicting reports concerning how central E6AP is to the global function of the HPV-16 and HPV-18 E6 oncoproteins. To investigate this further we have analysed the effects of E6AP removal upon the stability of endogenously expressed E6 protein. We show that when E6AP is silenced in HPV-positive cells, E6 protein levels are dramatically decreased in a proteasome-dependent manner. Further, we show that when E6AP is depleted in HeLa cells, E6 has a greatly decreased half-life. In addition, overexpression of E6AP stabilises ectopically expressed HPV-16 and HPV-18 E6 in a manner that is independent of its ubiquitin ligase activity. These results demonstrate that the stability of HPV E6 is critically dependent upon the presence of E6AP.
人乳头瘤病毒（HPV）E6癌蛋白靶向多种细胞蛋白，使其通过泛素介导的降解途径降解。就p53而言，这一过程由E6相关蛋白（E6AP）泛素连接酶介导。然而，关于E6AP在HPV - 16和HPV - 18 E6癌蛋白整体功能中的核心作用，存在相互矛盾的报道。为了进一步研究这一问题，我们分析了去除E6AP对内源性表达的E6蛋白稳定性的影响。我们发现，当在HPV阳性细胞中沉默E6AP时，E6蛋白水平以蛋白酶体依赖的方式显著降低。此外，我们还表明，当在HeLa细胞中耗尽E6AP时，E6的半衰期大幅缩短。另外，E6AP的过表达以一种独立于其泛素连接酶活性的方式稳定异位表达的HPV - 16和HPV - 18 E6。这些结果表明，HPV E6的稳定性严重依赖于E6AP的存在。
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