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

锚定依赖性新基因E6DG1功能分析

• 批准号: 14570116
• 负责人: SHIRASAWA Hiroshi
• 金额: $ 2.18万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570116/
• 关键词: anchorage dependence; HPV; E6; Rlp7p; ribosome related protein

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.

我们发现了一个新的基因，该基因的表达被人乳头瘤病毒16(HPVI6) E6蛋白下调，并命名为E6DG1。在本研究中，我们旨在分析E6DG1的功能。过表达E6DG1可抑制肿瘤细胞的锚定依赖性。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。据推测，与E6DG1相关的通路可能在HeLa细胞中受到干扰。E6DG1的过表达和下调均可诱导细胞凋亡。对E6DG1的分析表明该蛋白与核糖体蛋白相关，与60S L7具有同源性。E6DG1的结构域与酵母Rlp7p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Rlp7p一样，在核糖体的生物发生中具有关键功能。提示E6DG1是一种核糖体相关蛋白，参与核糖体生物发生过程，影响锚定依赖性。我们认为E6DG1也可能通过与细胞周期和凋亡的相互作用影响染色体的不稳定性。这种由干扰核糖体生物发生引起的染色体不稳定性的假设机制将为研究新的肿瘤发生机制提供新的见解。

项目成果

Komoda, F. et al.: "MEKK1 induces c-Jun complexes that act as negative regulators for cell survival and proliferation of HCC cells."Int.J.Oncol.. 21. 553-559 (2002)

Komoda, F. 等人：“MEKK1 诱导 c-Jun 复合物作为 HCC 细胞存活和增殖的负调节因子。”Int.J.Oncol.. 21. 553-559 (2002)

Survival regulation in pancreatic cancer cells by c-Jun.

c-Jun 对胰腺癌细胞的生存调节。

• 发表时间: 2003
• 期刊: Int.J.Oncol. 23
• 作者: Okutomi;Y. et al.
• 通讯作者: Y. et al.

Okutomi, Y. et al.: "Survival regulation in pancreatic cancer cells by c-Jun."Int.J.Oncol.. 23. 1127-1134 (2003)

Okutomi, Y. 等人：“c-Jun 对胰腺癌细胞的生存调节。”Int.J.Oncol.. 23. 1127-1134 (2003)

Lack of evidence for reovirus infection in tissues from patients with biliary atresia and congenital dilatation of the bile duct.

• DOI: 10.1016/j.jhep.2003.10.025
• 发表时间: 2003-04
• 期刊: Journal of hepatology
• 影响因子: 25.7
• 作者: T. Saito;K. Shinozaki;T. Matsunaga;T. Ogawa;T. Etoh;T. Muramatsu;K. Kawamura;H. Yoshida;N. Ohnuma;H. Shirasawa

Sakao, S. et al.: "Expression of the potential novel gene E6DG1 downregulated by the E6 protein of human papillomavirus type 16 is correlated with anchorage-independent growth."Int.J.Oncol.. 21. 237-279 (2002)

Sakao, S. 等人：“受人乳头瘤病毒 16 型 E6 蛋白下调的潜在新基因 E6DG1 的表达与锚定非依赖性生长相关。”Int.J.Oncol.. 21. 237-279 (2002)