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Gene Review

NDRG1  -  N-myc downstream regulated 1

Homo sapiens

Synonyms: CAP43, CMT4D, DRG-1, DRG1, Differentiation-related gene 1 protein, ...
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Disease relevance of NDRG1

  • We initially demonstrated that the expression of NDRG1 is enhanced in primary human trophoblasts exposed to hypoxia [1].
  • In addition, NDRG1 may be a putative tumor metastasis promoter gene and is regarded as one of the molecular biological markers that can forecast early metastasis of CRCs [2].
  • At the same time, the correlations of NDRG1 with sex, age of patients and histological types of colorectal carcinomas were observed [2].
  • Among the esophageal cancer tissues, NDRG1 mRNA expression was significantly lower in tumors of more advanced pathological stage (0-I vs. II-IV; P = 0.0027) and local tumor invasion (T1-2 vs. T3-4; P = 0.0136) [3].
  • Decreased expression of NDRG1 is correlated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma [3].

Psychiatry related information on NDRG1

  • The authors report a case that offers insight into the diagnostic challenges of "Munchausen Syndrome by Proxy." Initial presentation with history of fever and later with intractable vomiting led to invasive and expensive diagnostic evaluation before confirming the diagnosis [4].
  • RESULTS: Proxy respondents provided levels of complete information similar to index cases and controls for height and weight; occupational physical activity; consumption of coffee, alcohol, and cigarettes; and family history of cancer [5].
  • The importance of transference and countertransference in Munchausen Syndrome by Proxy [6].
  • Repeated false allegations of sexual abuse presenting to sheriffs: when is it Munchausen by Proxy [7]?
  • There would seem to be three motives for research into Munchausen Syndrome by Proxy (MSBP) abuse; first to enhance treatment; second to enhance our understanding of the psychopathology of those who carry out the abuse; and third to find interventions to prevent its occurrence [8].

High impact information on NDRG1

  • RESULTS: In the normal liver, hepatocytes expressed E-cadherin and a 129-kilodalton cadherin identified by the anti-N-cadherin antibody GC4 [9].
  • Its induction also depends on the cognate host disease resistance gene RPS2 and the NDR1 gene that is required for RPS2-specified resistance [10].
  • NDRG1 is ubiquitously expressed and has been proposed to play a role in growth arrest and cell differentiation, possibly as a signaling protein shuttling between the cytoplasm and the nucleus [11].
  • Taken together, these findings point to NDRG1 having a role in the peripheral nervous system, possibly in the Schwann-cell signaling necessary for axonal survival [11].
  • NDRG1 is an intracellular protein that is induced under a number of stress and pathological conditions, and it is thought to be associated with cell growth and differentiation [12].

Chemical compound and disease context of NDRG1


Biological context of NDRG1


Anatomical context of NDRG1


Associations of NDRG1 with chemical compounds


Physical interactions of NDRG1


Enzymatic interactions of NDRG1

  • SGK1 also phosphorylated the related NDRG1 isoform at Thr328, Ser330 and Thr346 (equivalent to Thr330, Ser332 and Thr348 of NDRG2), as well as Thr356 and Thr366 [18].

Regulatory relationships of NDRG1


Other interactions of NDRG1

  • These two genes, together with NDRG1 and a previously deposited cDNA (designated NDRG2), constitute the NDRG gene family [25].
  • Characterization of the human NDRG gene family: a newly identified member, NDRG4, is specifically expressed in brain and heart [25].
  • Consistent with these results, NDRG1 reduced the expression level of p53 in trophoblasts cultured in standard or hypoxic conditions [1].
  • 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 [16].
  • Expression analysis of the two selected ER stress responsive genes, NDRG1 and HERPUD1 in primary CaPs revealed a significantly reduced tumor associated expression [26].

Analytical, diagnostic and therapeutic context of NDRG1


  1. N-myc down-regulated gene 1 modulates the response of term human trophoblasts to hypoxic injury. Chen, B., Nelson, D.M., Sadovsky, Y. J. Biol. Chem. (2006) [Pubmed]
  2. Correlation of N-myc downstream-regulated gene 1 overexpression with progressive growth of colorectal neoplasm. Wang, Z., Wang, F., Wang, W.Q., Gao, Q., Wei, W.L., Yang, Y., Wang, G.Y. World J. Gastroenterol. (2004) [Pubmed]
  3. Decreased expression of NDRG1 is correlated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma. Ando, T., Ishiguro, H., Kimura, M., Mitsui, A., Kurehara, H., Sugito, N., Tomoda, K., Mori, R., Takashima, N., Ogawa, R., Fujii, Y., Kuwabara, Y. Dis. Esophagus (2006) [Pubmed]
  4. Ipecac toxicity in "Munchausen syndrome by proxy". Bader, A.A., Kerzner, B. Therapeutic drug monitoring. (1999) [Pubmed]
  5. Utility of Proxy versus Index Respondent Information in a Population-Based Case-Control Study of Rapidly Fatal Cancers. Campbell, P.T., Sloan, M., Kreiger, N. Annals of epidemiology (2007) [Pubmed]
  6. The importance of transference and countertransference in Munchausen Syndrome by Proxy. Pompili, M., Mancinelli, I., Girardi, P., Ruberto, A., Tatarelli, R. Child abuse & neglect. (2003) [Pubmed]
  7. Repeated false allegations of sexual abuse presenting to sheriffs: when is it Munchausen by Proxy? Schreier, H.A. Child abuse & neglect. (1996) [Pubmed]
  8. Concerns about research and prevention strategies in Munchausen Syndrome by Proxy (MSBP) abuse. Eminson, M., Jureidini, J. Child abuse & neglect. (2003) [Pubmed]
  9. Expression of cadherins and alpha-catenin in primary epithelial tumors of the liver. Kozyraki, R., Scoazec, J.Y., Flejou, J.F., D'Errico, A., Bedossa, P., Terris, B., Fiorentino, M., Bringuier, A.F., Grigioni, W.F., Feldmann, G. Gastroenterology (1996) [Pubmed]
  10. A pathogen-inducible endogenous siRNA in plant immunity. Katiyar-Agarwal, S., Morgan, R., Dahlbeck, D., Borsani, O., Villegas, A., Zhu, J.K., Staskawicz, B.J., Jin, H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom. Kalaydjieva, L., Gresham, D., Gooding, R., Heather, L., Baas, F., de Jonge, R., Blechschmidt, K., Angelicheva, D., Chandler, D., Worsley, P., Rosenthal, A., King, R.H., Thomas, P.K. Am. J. Hum. Genet. (2000) [Pubmed]
  12. Ndrg1-deficient mice exhibit a progressive demyelinating disorder of peripheral nerves. Okuda, T., Higashi, Y., Kokame, K., Tanaka, C., Kondoh, H., Miyata, T. Mol. Cell. Biol. (2004) [Pubmed]
  13. 17Beta-estradiol induces down-regulation of Cap43/NDRG1/Drg-1, a putative differentiation-related and metastasis suppressor gene, in human breast cancer cells. Fotovati, A., Fujii, T., Yamaguchi, M., Kage, M., Shirouzu, K., Oie, S., Basaki, Y., Ono, M., Yamana, H., Kuwano, M. Clin. Cancer Res. (2006) [Pubmed]
  14. The impact of single cysteine residue mutations on the replication terminator protein. Vivian, J.P., Hastings, A.F., Duggin, I.G., Wake, R.G., Wilce, M.C., Wilce, J.A. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  15. NDRG1 is necessary for p53-dependent apoptosis. Stein, S., Thomas, E.K., Herzog, B., Westfall, M.D., Rocheleau, J.V., Jackson, R.S., Wang, M., Liang, P. J. Biol. Chem. (2004) [Pubmed]
  16. Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family. Qu, X., Zhai, Y., Wei, H., Zhang, C., Xing, G., Yu, Y., He, F. Mol. Cell. Biochem. (2002) [Pubmed]
  17. Comparative proteomic analysis of hypoxia-treated and untreated human leukemic U937 cells. Han, Y.H., Xia, L., Song, L.P., Zheng, Y., Chen, W.L., Zhang, L., Huang, Y., Chen, G.Q., Wang, L.S. Proteomics (2006) [Pubmed]
  18. Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3. Murray, J.T., Campbell, D.G., Morrice, N., Auld, G.C., Shpiro, N., Marquez, R., Peggie, M., Bain, J., Bloomberg, G.B., Grahammer, F., Lang, F., Wulff, P., Kuhl, D., Cohen, P. Biochem. J. (2004) [Pubmed]
  19. Cap43, a novel gene specifically induced by Ni2+ compounds. Zhou, D., Salnikow, K., Costa, M. Cancer Res. (1998) [Pubmed]
  20. Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage. Kurdistani, S.K., Arizti, P., Reimer, C.L., Sugrue, M.M., Aaronson, S.A., Lee, S.W. Cancer Res. (1998) [Pubmed]
  21. Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer. Guan, R.J., Ford, H.L., Fu, Y., Li, Y., Shaw, L.M., Pardee, A.B. Cancer Res. (2000) [Pubmed]
  22. Downregulation of Cap43 gene by von Hippel-Lindau tumor suppressor protein in human renal cancer cells. Masuda, K., Ono, M., Okamoto, M., Morikawa, W., Otsubo, M., Migita, T., Tsuneyoshi, M., Okuda, H., Shuin, T., Naito, S., Kuwano, M. Int. J. Cancer (2003) [Pubmed]
  23. Overexpression of NDRG1 is an indicator of poor prognosis in hepatocellular carcinoma. Chua, M.S., Sun, H., Cheung, S.T., Mason, V., Higgins, J., Ross, D.T., Fan, S.T., So, S. Mod. Pathol. (2007) [Pubmed]
  24. The growth-inhibitory Ndrg1 gene is a Myc negative target in human neuroblastomas and other cell types with overexpressed N- or c-myc. Li, J., Kretzner, L. Mol. Cell. Biochem. (2003) [Pubmed]
  25. Characterization of the human NDRG gene family: a newly identified member, NDRG4, is specifically expressed in brain and heart. Zhou, R.H., Kokame, K., Tsukamoto, Y., Yutani, C., Kato, H., Miyata, T. Genomics (2001) [Pubmed]
  26. Androgen-induced expression of endoplasmic reticulum (ER) stress response genes in prostate cancer cells. Segawa, T., Nau, M.E., Xu, L.L., Chilukuri, R.N., Makarem, M., Zhang, W., Petrovics, G., Sesterhenn, I.A., McLeod, D.G., Moul, J.W., Vahey, M., Srivastava, S. Oncogene (2002) [Pubmed]
  27. Mutation screening of the N-myc downstream-regulated gene 1 (NDRG1) in patients with Charcot-Marie-Tooth Disease. Hunter, M., Bernard, R., Freitas, E., Boyer, A., Morar, B., Martins, I.J., Tournev, I., Jordanova, A., Guergelcheva, V., Ishpekova, B., Kremensky, I., Nicholson, G., Schlotter, B., Lochmüller, H., Voit, T., Colomer, J., Thomas, P.K., Levy, N., Kalaydjieva, L. Hum. Mutat. (2003) [Pubmed]
  28. Phosphorylation of RTP, an ER stress-responsive cytoplasmic protein. Agarwala, K.L., Kokame, K., Kato, H., Miyata, T. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  29. Cellular differentiation determines the expression of the hypoxia-inducible protein NDRG1 in pancreatic cancer. Angst, E., Sibold, S., Tiffon, C., Weimann, R., Gloor, B., Candinas, D., Stroka, D. Br. J. Cancer (2006) [Pubmed]
  30. Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes. Kokame, K., Kato, H., Miyata, T. J. Biol. Chem. (1996) [Pubmed]
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