Molecular and Cellular Biochemistry

, Volume 229, Issue 1, pp 35–44

Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family

  • Xianghu Qu
  • Yun Zhai
  • Handong Wei
  • Chenggang Zhang
  • Guichun Xing
  • Yongtao Yu
  • Fuchu He
Article

DOI: 10.1023/A:1017934810825

Cite this article as:
Qu, X., Zhai, Y., Wei, H. et al. Mol Cell Biochem (2002) 229: 35. doi:10.1023/A:1017934810825

Abstract

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 α/β 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.

NDRG gene familyα/β hydrolase folddifferentiationtissue distributionsubcellular localizationphylogenetic tree

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Xianghu Qu
    • 1
  • Yun Zhai
    • 1
  • Handong Wei
    • 1
  • Chenggang Zhang
    • 1
  • Guichun Xing
    • 1
  • Yongtao Yu
    • 1
  • Fuchu He
    • 1
  1. 1.Department of Genomics and Proteomics, Beijing Institute of Radiation MedicineChinese National Human Genome Center at BeijingBeijingChina