Vaeteewoottacharn Kulthida, Chamutpong Siriphatr, Ponglikitmongkol Mathurose, Angeletti Peter C
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
Virol J. 2005 Jun 16;2:50. doi: 10.1186/1743-422X-2-50.
High-risk Human Papillomavirus (HPV) is the etiological agent associated with the majority of anogenital cancers. The primary HPV oncogenes, E6 and E7, undergo a complex splicing program resulting in protein products whose purpose is not fully understood. Previous mouse studies have confirmed the existence of a translated product corresponding to the E6I splice product. In terms of function, the translated E6I protein has been shown to bind to E6 protein and to E6 associated protein (E6AP). E6I has an inhibitory effect on E6-mediated p53 degradation in E6 expressing cells. In order to analyze the relationship between E6I and full-length E6 in relation to localization, we created a series of green fluorescent protein (GFP) fusion products. The localization of these proteins with reference to E6AP in vivo remains unclear. Therefore, we investigated the cellular distribution of different forms of E6 with reference to E6AP. E6 and E6I proteins, expressed from a wild type E6 gene cassette, were dispersed in the nucleus and the cytoplasm. Whereas, the E6 splice donor mutant (E6MT) was primarily localized to the nucleus. E6I protein and E6AP were found to co-localize mainly to the cytoplasm, whereas the co-localization of full-length E6 protein and E6AP, if at all, was found mainly at the perinuclear region. These results suggest a functional relationship between the E6*I and full-length E6 protein which correlates with their localization and likely is important in regulation of the E6-E6AP complex.
高危型人乳头瘤病毒（HPV）是与大多数肛门生殖器癌相关的病原体。主要的HPV癌基因E6和E7经历复杂的剪接程序，产生的蛋白质产物其作用尚未完全明确。先前的小鼠研究已证实存在与E6I剪接产物相对应的翻译产物。就功能而言，已表明翻译后的E6I蛋白可与E6蛋白及E6相关蛋白（E6AP）结合。E6I对E6表达细胞中E6介导的p53降解具有抑制作用。为了分析E6I与全长E6在定位方面的关系，我们构建了一系列绿色荧光蛋白（GFP）融合产物。这些蛋白在体内相对于E6AP的定位仍不清楚。因此，我们参照E6AP研究了不同形式E6的细胞分布。由野生型E6基因盒表达的E6和E6I蛋白分散于细胞核和细胞质中。而E6剪接供体突变体（E6MT）主要定位于细胞核。发现E6I蛋白和E6AP主要共定位于细胞质，而全长E6蛋白与E6AP的共定位（如果有的话）主要见于核周区域。这些结果表明E6*I与全长E6蛋白之间存在功能关系，这与其定位相关，并且可能在E6 - E6AP复合物的调控中起重要作用。
