人分化相关基因Ndr2的克隆与组织表达谱研究

Cloning and Tissue Expression of the Novel Human Differentiation-related Gene Ndr2

人Ndr1基因参与细胞终末分化 ,并且对肿瘤细胞增殖和肿瘤转移具有抑制作用 .从人 2 2周孕龄胎肝cDNA文库中获得与人Ndr1基因同源的一段表达性序列标签 ,继而从成人脑cDNA文库分离出其全长cDNA(2 12 1bp) ,并将该基因命名为Ndr2 .其染色体定位为 14q11 1- 11 2 ,开放阅读框编码 371个氨基酸 ,且与NDR1蛋白一样 ,含有一个典型的α β水解酶折叠类结构域 (α βhydrolasefold) .Northern杂交和点杂交分析显示 ,该基因与Ndr1一样 ,在脑中高表达 ,在胚胎组织的表达较低 ,在 8种人肿瘤细胞中的表达极低 .然而 ,Ndr2基因的组织表达谱与Ndr1又有鲜明的差异 :其在成人骨骼肌和脑等神经组织中表达最高 ,在唾液腺、肝、肾、心肌和气管中的表达次之 .结果提示 ,NDR2具有与NDR1相似或相关的重要功能 .

The differentiation-related gene Ndr1 (N-Myc downstream regulated) is upregulated during cell differentiation, and repressed by N-myc and c-myc in several tumor cells. The function of NDRG1 in the peripheral nervous system is necessary for axonal survival. The human cDNA encoding NDRG2(371amino acid residues), which is homologous to NDRG1,was cloned. At the amino acid level, the two genes shared 53% identity. Both proteins contained an α/β hydrolase fold as in human lysosomal acid lipase. Based on UniGene cluster searching, the gene for Ndr2 was located at chromosome 14q11.1-11.2. Northern and dot blot analyses showed that the gene was highly expressed in adult brain, very lowly expressed in fetal tissues and almost not detected in the eight human cancer lines. In addition, NDRG2 was highly expressed in adult skeletal muscle and brain. The results suggest that NDRG2 and NDRG1 might display similar or related specific functions in distinct tissues.