Molecular and Cellular Biochemistry

, Volume 229, Issue 1–2, pp 35–44 | Cite as

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

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 family α/β hydrolase fold differentiation tissue distribution subcellular localization phylogenetic tree 

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References

  1. 1.
    Shimono A, Okuda T, Kondoh H: N-myc-dependent repression of ndr1, a gene identified by direct subtraction of whole mouse embryo cDNAs between wild type and N-myc mutant. Mech Dev 83: 39–52, 1999Google Scholar
  2. 2.
    Kokame K, Kato H, Miyata T: Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes. J Biol Chem 271: 29659–29665, 1996Google Scholar
  3. 3.
    Ulrix W, Swinnen JV, Heyns W, Verhoeven G: The differentiation-related gene 1, Drg1, is markedly upregulated by androgens in LNCaP prostatic adenocarcinoma cells. FEBS Lett 455: 23–26, 1999Google Scholar
  4. 4.
    Piquemal D, Joulia D, Balaguer P, Basset A, Marti J, Commes T: Differential expression of the RTP/Drg1/Ndr1 gene product in proliferating and growth arrested cells. Biochim Biophys Acta 1450: 364–373, 1999Google Scholar
  5. 5.
    Kurdistani SK, Arizti P, Reimer CL, Sugrue MM, Aaronson SA, Lee SW: Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage. Cancer Res 58: 4439–4444, 1998Google Scholar
  6. 6.
    Zhou D, Salnikow K, Costa M: Cap43, a novel gene specifically induced by Ni2+ compounds. Cancer Res 58: 2182–2189, 1998Google Scholar
  7. 7.
    Guan RJ, Ford HL, Fu Y, Li Y, Shaw LM, Pardee AB: Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer. Cancer Res 60:749–755, 2000Google Scholar
  8. 8.
    Kalaydjieva L, Gresham D, Gooding R, Heather L, Baas F, de Jonge R, Blechschmidt K, Angelicheva D, Chandler D, Worsley P, Rosenthal A, King RH, Thomas PK: N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom. Am J Hum Genet 67: 47–58, 2000Google Scholar
  9. 9.
    Kalaydjieva L, Nikolova A, Turnev I, Petrova J, Hristova A, Ishpekova B, Petkova I, Shmarov A, Stancheva S, Middleton L, Merlini L, Trogu A, Muddle JR, King RH, Thomas PK: Hereditary motor and sensory neuropathy — Lom, a novel demyelinating neuropathy associated with deafness in gypsies. Clinical, electrophysiological and nerve biopsy findings. Brain 121: 399–408, 1998Google Scholar
  10. 10.
    Okuda T, Kondoh H: Identification of new genes ndr2 and ndr3 which are related to Ndr1/RTP/Drg1 but show distinct tissue specificity and response to N-myc. Biochem Biophys Res Commun 266: 208–215, 1999Google Scholar
  11. 11.
    Lin TM, Chang C: Cloning and characterization of TDD5, an androgen target gene that is differentially repressed by testosterone and dihydrotestosterone. Proc Natl Acad Sci USA 94: 4988–4993, 1997Google Scholar
  12. 12.
    Yamauchi Y, Hongo S, Ohashi T, Shioda S, Zhou C, Nakai Y, Nishinaka N, Takahashi R, Takeda F, Takeda M: Molecular cloning and characterization of a novel developmentally regulated gene, Bdm1, showing predominant expression in postnatal rat brain. Brain Res Mol Brain Res 68: 149–158, 1999Google Scholar
  13. 13.
    Wu CT, Pei XT, Cong PJ: Effects of human fetal liver extract on the growth of HL-60 cells. Exp Hematol 17: 304–308, 1989Google Scholar
  14. 14.
    Zhao SF, Wu CT: Comparison of the hemopoietic growth factors produced during in vitro culture of murine and human fetal liver. Exp Hematol 18: 367–371, 1990Google Scholar
  15. 15.
    He FC, Wu CT, Tu Q, Xing GC: Human hepatic stimulatory substance: A product of gene expression of human fetal liver tissue. Hepatology 17: 225–229, 1993Google Scholar
  16. 16.
    Wang G, Yang XM, Zhang Y, Wang QM, Chen HP, Wei HD, Xing GC, Xie L, Zhang CG, Fang DC, Wu CT, He FC: Identification and characterization of receptor for mammalian hepatopoietin that is homologous to yeast ERV1. J Biol Chem 274: 11469–11472, 1999Google Scholar
  17. 17.
    Zhang C, Yu Y, Zhang S, Liu M, Xing G, Wei H, Bi J, Liu X, Zhou G, Dong C, Hu Z, Zhang Y, Luo L, Wu C, Zhao S, He F: Characterization, chromosomal assignment, and tissue expression of a novel human gene belong to ARF GAP family. Genomics 63: 400–408, 2000Google Scholar
  18. 18.
    Qu XH, Zhang CG, Zhai Y, Xing GC, Wei HD, Yu YT, Wu SF, He FC: Characterization and tissue expression of a novel human gene npdc1. Gene 264: 37–44, 2001Google Scholar
  19. 19.
    Ollis DL, Cheah E, Cygler M, Dijkstra B, Frolow F, Franken SM, Harel M, Remington SJ, Silman I, Schrag J Sussman JL, Verschueren KHG, Goldman A: The alpha/beta hydrolase fold. Protein Eng 5: 197–211, 1992Google Scholar
  20. 20.
    Schultz J, Copley RR, Doerks T, Ponting CP, Bork P: SMART: A Webbased tool for the study of genetically mobile domains. Nucleic Acids Res 28: 231–234, 2000Google Scholar
  21. 21.
    Hofmann K, Bucher P, Falquet L, Bairoch A: The PROSITE database, its status in 1999. Nucleic Acids Res 27: 215–219, 1999Google Scholar
  22. 22.
    Kozak M: Initiation of translation in prokaryotes and eukaryotes. Gene 234: 187–208, 1999Google Scholar
  23. 23.
    Zhou RH, Kokame K, Tsukamoto Y, Yutani C, Kato H, Miyata T: Characterization of the human ndrg gene family: A newly identified member, ndrg4, is specifically expressed in brain and heart. Genomics 73: 86–97, 2001Google Scholar
  24. 24.
    van Belzen N, Dinjens WN, Diesveld MP, Groen NA, van der Made AC, Nozawa Y, Vlietstra R, Trapman J, Bosman FT: A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms. Lab Invest 77: 85–92, 1997Google Scholar

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

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