酵母LAG1同源的人类长寿保障新基因LASS2的克隆和功能研究

Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene lag1

目的 分离和克隆肝癌相关基因。方法 我们用高通量功能筛选和RACE(rapidamplificationofcDNAends)方法从人肝cDNA文库中克隆到一个与酵母长寿保障基因LAG1高度同源的人类新基因LASS2 (homosapienslongevityassurancehomologue 2ofyeastLAG1)。结果 LASS2在正常人肝组织和肾组织中高表达 ,其表达谱不同于早先在人中克隆到的另一个与酵母LAG1高度同源的人类长寿保障基因LAG1Hs- 1。放射杂交基因定位显示LASS2位于人类染色体 1q11,酵母双杂交和GST结合实验发现LASS2蛋白能与细胞中的几个膜相关受体或转运体相互作用 ;另外 ,LASS2在体外对人肝癌细胞的克隆形成具有抑制作用 ,提示该基因可能参与细胞的生长调控。结论 LASS2是一个新的肝癌相关基因。

Objective To islate and clone the HCC-related genes. Methods We have identified the LASS2 gene, a novel human homolog of yeast LAG1 longevity gene. Results The LASS2 transcript is highly expressed in liver and kidney, which is quite different from the previously identified human LAG1 homolog LAG1Hs-1. Radiation hybrid mapping studies indicated that the LASS2 gene is located at chromosome 1q11. Yeast two-hybrid screening and glutathione S-transferase (GST) pulldown assays revealed that the LASS2 protein interacts with several membrane-associated receptors or transporters. Furthermore, our studies has shown that LASS2 is able to inhibit the colony formation of human hepatoma cells in vitro, which provide a clue to link this gene to the regulation of cell growth. Conclusion LASS2 is a novel HCC-related gene.