Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family.
NDRG1 (N-Myc downstream regulated) is upregulated during cell differentiation, repressed by N-myc and c-myc in embryonic cells, and suppressed in several tumor cells. A nonsense mutation in the NDRG1 gene has been reported to be causative for hereditary motor and sensory neuropathy-Lom (HMSNL), indicating that NDRG1 functions in the peripheral nervous system necessary for axonal survival. Here, we cloned three human cDNAs encoding NDRG2 (371aa), NDRG3 (375aa) and NDRG4 (339aa), which are homologous to NDRG1. These three genes, together with NDRG1, constitute the NDRG gene family. The phylogenetic analysis of the family demonstrated that human NDRG1 and NDRG3 belong to a subfamily, and NDRG2 and NDRG4 to another. At amino acid (aa) level, the four members share 53-65% identity. Each of the four proteins contains an alpha/beta hydrolase fold as in human lysosomal acid lipase. Expression of the fusion proteins NDRG2/GFP, NDRG3/GFP and NDRG4/GFP in COS-7 cells showed that all of them are cytosolic proteins. Based on UniGene cluster analysis, the genes NDRG2, NDRG3 and NDRG4 are located at chromosome 14q11.1-11.2, 20q12-11.23 and 16q21-22.1, respectively. Northern and dot blot analysis shows that all of the three genes are highly expressed in adult brain and almost not detected in the eight human cancer lines. In addition, in contrast to the relatively ubiquitous expression of NDRG1, NDRG2 is highly expressed in adult skeletal muscle and brain, NDRG3 highly expressed in brain and testis, and NDRG4 specifically expressed in brain and heart, suggesting that they might display different specific functions in distinct tissues.
Qu
Xianghu
X
Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Chinese National Human Genome Center at Beijing.
Zhai
Yun
Y
Wei
Handong
H
Zhang
Chenggang
C
Xing
Guichun
G
Yu
Yongtao
Y
He
Fuchu
F
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D019556:COS Cells; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002874:Chromosome Mapping; D049452:Green Fluorescent Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D009124:Muscle Proteins / Q000235:genetics* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D010802:Phylogeny; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D025521:Tumor Suppressor Proteins
D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D009124:Muscle Proteins; C466228:NDRG2 protein, human; C431706:NDRG3 protein, human; C431705:NDRG4 protein, human; D009419:Nerve Tissue Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins