Research of a multi-stage hepatocaranogenesis by use of gankyrn tranggenic mice.

Gankyrin在人肝细胞癌中过表达。其过表达导致MH-3 T3细胞转化并在裸鼠中诱导肿瘤形成。Ite过表达与pRB蛋白的过度磷酸化和降解相关。Gankyrin已显示结合细胞周期蛋白D依赖性激酶4，其底物之一是pRB。在酵母双杂交筛选中还发现Gankyrin与26 S蛋白酶体的19 S调节复合物的人S6 b ATP酶亚基形成复合物。另一种与Gankyrin相互作用的蛋白质是黑色素瘤抗原MACE-A4。薄相互作用抑制gankyrin的致癌活性。Gankyrin的表达在肝切除术后或暴发性肝炎后的肝再生过程中增加。MAGE-A4被加工以产生104个氨基酸的C-末端片段，并诱导肿瘤细胞中的p53依赖性或非依赖性凋亡。Gankyrin过表达作为E3辅因子发挥作用，并导致肿瘤抑制因子的蛋白质降解。我们构建了一个Gankyrin转基因小鼠，使用HBV衍生的启动子和增强这些小鼠在肝脏中表达低水平的Gankyrin蛋白。然而，它表明，他们有肿瘤在肝脏。

Gankyrin is overexpressed in human hepatocellular carcinomas. Its overexpression leads to transformation of MH-3T3 cells and induces tumor formation in nude mice. Ite overexpression correlates with hyperphosphorylation and degradation of pRB protein. Gankyrin has been shown to bind to cyclin D-dependent kinase 4, one of whose substrates is pRB. Gankyrin has also been found in yeast two-hybrid screens to form a complex with the human S6b ATPase subunit of the 19S regulatory complex of the 26S proteasome. The other protein shown to interact with gankyrin is a melanoma antigen MACE-A4. Thin interaction suppresses the oncogenic activity of gankyrin. Gankyrin expression was shown to increase during liver regeneration after hepatic resection or fuluminant hepatitis. MAGE-A4 was processed to generate a C-terminal fragment of 104 amino acids, and induced p53-dependent or independent apoptosis in tumour cells. Gankyrin overexpression functions as a E3 cofactors and leads to protein degradation of the tumour suppressors. We constructed a gankyrin-transgenic mouse, using HBV-derived promoter and enhances These mice expressed low levels of gankyrin protein in the livers. However, it is shown that they have tumors in the livers.