The analysis of a novel gene E6DG1 function involving in anchorage dependency

我们发现了一个新基因，该基因的表达受人乳头瘤病毒16型(HPVI6)E6蛋白下调，命名为E6DG1。在这项研究中，我们旨在分析E6DG1的功能。E6DG1的过表达抑制了癌细胞的锚定依赖性。相反，E6DG1的下调导致几种癌细胞的锚定依赖性增强，而对HeLa细胞的锚定依赖性没有影响。推测在HeLa细胞中参与E6DG1的通路可能受到干扰。E6DG1的高表达和低表达均可诱导细胞凋亡，对E6DG1的分析表明该蛋白与核糖体蛋白相关，与60L7同源。E6DG1的结构域与酵母Rlp7p中发现的结构域相似，Rlp7p是一种核糖体蛋白相关蛋白。我们的分析表明，E6DG1与酵母Rlp7一样，在核糖体的生物发生过程中具有关键的功能。这表明E6DG1是一种与核糖体相关的蛋白质，参与了核糖体生物发生的过程，影响了锚定依赖性。我们认为E6DG1也可能通过与细胞周期和细胞凋亡的相互作用而影响染色体的不稳定性。这种通过干扰核糖体生物发生而导致染色体不稳定的假想机制将为肿瘤发生的新机制提供一个新的视角。

We identified a novel gene, the expression of which is downregulated by the human papillomavirus 16(HPVI6) E6 protein, and designated E6DG1. In this study, we aimed at the analysis of the E6DG1 functions.The overexpression of the E6DG1 suppressed the anchorage dependency of cancer cells. In contrast, the downregulation of E6DG1 caused the enhancement of the anchorage dependency of several cancer cells, and had no effect on the anchorage dependency of HeLa cells. It was supposed that the pathway involved in E6DG1 may be disturbed in HeLa cells. Both the overexpression and downregulation of E6DG1 also induced apoptosis.The analysis of E6DG1 revealed that this protein is ribosomal protein related and has homology to 60S L7. The E6DG1 has a domain which is similar to that found in yeast Rlp7p, a ribosomal protein related protein. Our analysis indicated that the E6DG1 has a critical function involved in the biogenesis of ribosome as the yeast Rlp7p.It was suggested that the E6DG1 is a ribosome-related protein involving in the processing of the ribosome biogenesis, affecting the anchorage dependency. We propose that the E6DG1 might also affect the chromosomal instability through interacting with the cell cycle and apoptosis. This supposed mechanism of the chromosomal instability induced by disturbing the ribosomal biogenesis would provide an insight into a novel mechanism of oncogenesis.