# NDRG1

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Protein-coding gene in the species Homo sapiens

NDRG1 Identifiers Aliases NDRG1, CAP43, CMT4D, DRG-1, DRG1, GC4, HMSNL, NDR1, NMSL, PROXY1, RIT42, RTP, TARG1, TDD5, N-myc downstream regulated 1 External IDs OMIM: 605262; MGI: 1341799; HomoloGene: 55953; GeneCards: NDRG1; OMA:NDRG1 - orthologs Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8q24.22 Start 133,237,175 bp[1] End 133,302,022 bp[1] Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 D2 Start 66,801,167 bp[2] End 66,841,489 bp[2] RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in olfactory bulb internal globus pallidus tibial nerve corpus callosum inferior olivary nucleus skin of abdomen inferior ganglion of vagus nerve trigeminal ganglion skin of leg C1 segment Top expressed in sciatic nerve epithelium of lens human kidney migratory enteric neural crest cell right kidney proximal tubule suprachiasmatic nucleus utricle ciliary body iris More reference expression data BioGPS More reference expression data Gene ontology Molecular function microtubule binding cadherin binding protein binding gamma-tubulin binding Cellular component cytoplasm centrosome membrane microtubule cytoskeleton myelin sheath plasma membrane microtubule organizing center recycling endosome membrane perinuclear region of cytoplasm microtubule extracellular exosome cytoskeleton nucleus cytosol glutamatergic synapse Biological process mast cell activation peripheral nervous system myelin maintenance DNA damage response, signal transduction by p53 class mediator response to metal ion positive regulation of spindle checkpoint regulation of cell population proliferation cellular response to hypoxia negative regulation of cell population proliferation regulation of apoptotic process signal transduction postsynapse organization Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez 10397 17988 Ensembl ENSG00000104419 ENSMUSG00000005125 UniProt Q92597 Q62433 RefSeq (mRNA) NM_001135242 NM_001258432 NM_001258433 NM_006096 NM_001374844 NM_001374845 NM_001374846 NM_001374847 NM_008681 RefSeq (protein) NP_001128714 NP_001245361 NP_001245362 NP_006087 NP_001361773 NP_001361774 NP_001361775 NP_001361776 NP_032707 Location (UCSC) Chr 8: 133.24 – 133.3 Mb Chr 15: 66.8 – 66.84 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse

**Protein NDRG1** is a [protein](/source/Protein) that in humans is encoded by the *NDRG1* [gene](/source/Gene).[5][6][7][8]

This gene is a member of the [N-myc](/source/N-Myc) downregulated gene family which belongs to the alpha/beta [hydrolase](/source/Hydrolase) superfamily. The protein encoded by this gene is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation[9]. Mutations in this gene have been reported to be causative the autosomal-recessive version of Charcot-Marie-Tooth disease known as CMT4D.[8]

It has been reported that NDRG1 localizes to the endosomes and is a [Rab4a](/source/RAB4A) effector involved in vesicular recycling.[10]

As reviewed by Fang et al.,[11] NDRG1 is involved in embryogenesis and development, cell growth and differentiation, lipid biosynthesis and myelination, stress responses, immunity, DNA repair and [cell adhesion](/source/Cell_adhesion) among other functions. NDRG1 is localised in the [cytoplasm](/source/Cytoplasm), nucleus and mitochondrion, at probabilities of 47.8%, 26.1% and 8.7%, respectively. In response to DNA damage NDRG1 translocates from the cytoplasm to the nucleus, where it may inhibit cell growth and promote DNA repair mechanisms. It is suggested that NDRG1 acts as a stress response gene or potentially as a [transcription factor](/source/Transcription_factor).

## Gene

In humans, *NDRG1* gene is located on the long arm of [chromosome 8](/source/Chromosome_8) (8q24.22). The gene encodes a 3.0 kilobases (kb) [messenger RNA](/source/Messenger_RNA) (mRNA) composed of 394 amino acids. NDRG1 belong to the NDRG1 family consisting of four members - NDRG1, [NDRG2](/source/NDRG2), NDRG3 and [NDRG4](/source/NDRG4) - that share a 53-65 % homology. In contrast to other family members, *NDRG1* has a three tandem (GTRSRSHTSE) repeats in the C-terminal part.[12][13]

The expression of *NDRG1* is regulated by hypoxia dependent and independent manner. Under hypoxia the oxygen sensor [hypoxia-inducible factor (HIF)-1α](/source/HIF1A) is translocated from cytoplasma to nucleus, where binds to HIF-1β to form HIF-1 complex. This complex works as a transcription factor, binds to hypoxia response element (HRE) in the promoter of hypoxia-related genes, one of these genes is the *NDRG1*.[14] Also heavy metal ions (nickel, cobalt, iron) upregulate NDRG1 by mimicking hypoxia. Opposite effect on *NDRG1* expression could have [myc oncoproteins](/source/Myc), [N-myc](/source/N-Myc) and [c-myc](/source/C-myc), which transcriptionally repress the expression. These effect is mediated indirectly by decreasing its promoter activity.[11]

## Role in cancer

As reviewed by Villodre et al., NDRG1 plays a dual role in [breast cancer](/source/Breast_cancer). NDRG1 was first to be known as tumor suppressor, but ongoing evidence suggested that NDRG1 could promote cancer [cell proliferation](/source/Cell_proliferation), invasion, migration, and [brain metastasis](/source/Brain_metastasis).[15] As reviewed by Kovacevic et al.,[16] NDRG1 is a potent, iron-regulated growth and [metastasis suppressor](/source/Metastasis_suppressor) that was found to be negatively correlated with cancer progression in a number of tumors, including [prostate](/source/Prostate_cancer), [pancreatic](/source/Pancreatic_cancer), [breast](/source/Breast_cancer), and [colon cancers](/source/Colorectal_cancer). NDRG1 has marked anti-oncogenic activity, being associated with decreased cell proliferation, migration, invasion, and angiogenesis. The molecular functions of NDRG1 affect numerous signaling pathways that regulate cancer cell proliferation, invasion, angiogenesis, and migration. Specifically, NDRG1 inhibits the oncogenic RAS, [c-Src](/source/Proto-oncogene_tyrosine-protein_kinase_Src), [phosphatidylinositol 3-kinase](/source/Phosphatidylinositol_3-kinase) (PI3K), [WNT](/source/Wnt_signaling_pathway), [ROCK1](/source/ROCK1)/pMLC2, and nuclear factor-light chain enhancer of activated B cell (NF-B) pathways, while promoting expression of key tumor-suppressive molecules including [phosphatase](/source/Phosphatase) and tensin homolog, [E-cadherin](/source/E-cadherin), and [mothers against decapentaplegic homolog 4](/source/Mothers_against_decapentaplegic_homolog_4) (SMAD4). Through its effects on E-cadherin and beta-catenin, which form the adherens junction and promote cell adhesion, NDRG1 also inhibits the epithelial to mesenchymal transition, an initial key step in metastasis.

## Functions in DNA repair and aging

In one of its functions at a molecular level, NDRG1 binds and stabilizes methyltransferases, chiefly [O-6-methylguanine-DNA methyltransferase](/source/O-6-methylguanine-DNA_methyltransferase) (MGMT),[17] a DNA repair protein. Thus, higher expression of NDRG1 can promote MGMT protein stability and activity. Dominick et al.[18] showed NDRG1 and MGMT protein expression was increased by 2-fold to 3-fold for each of three strains of mice (Snell, GHKRO, and PAPPA-KO) with increased longevity. These authors strongly suggest a link between the increase in the MGMT DNA repair pathway and a delay in the aging process in these mouse strains. This is consistent with the [DNA damage theory of aging](/source/DNA_damage_theory_of_aging).

## Role in immune system

The NDRG1 plays an important role in allergy and anaphylaxis, defence against bacterial pathogens and bacterial clearance, inflammation and wound healing. In mast cells, NDRG1 is upregulated during maturation and helps to rapid degranulation, which leads to enhanced exocytosis in response to various stimuli.[19] Also was shown its role in T-cell clonal anergy downstream of Egr2, where NDRG1 is upregulated in the absence of costimulation to inhibit subsequent re-activation of T cells by TCR and CD28 signaling.[20]

## References

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## Further reading

- Kovacevic Z, Richardson DR (December 2006). "The metastasis suppressor, Ndrg-1: a new ally in the fight against cancer". *Carcinogenesis*. **27** (12): 2355–66. [doi](/source/Doi_(identifier)):[10.1093/carcin/bgl146](https://doi.org/10.1093%2Fcarcin%2Fbgl146). [PMID](/source/PMID_(identifier)) [16920733](https://pubmed.ncbi.nlm.nih.gov/16920733).

- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". *Gene*. **138** (1–2): 171–4. [doi](/source/Doi_(identifier)):[10.1016/0378-1119(94)90802-8](https://doi.org/10.1016%2F0378-1119%2894%2990802-8). [PMID](/source/PMID_(identifier)) [8125298](https://pubmed.ncbi.nlm.nih.gov/8125298).

- Kalaydjieva L, Hallmayer J, Chandler D, Savov A, Nikolova A, Angelicheva D, et al. (October 1996). "Gene mapping in Gypsies identifies a novel demyelinating neuropathy on chromosome 8q24". *Nature Genetics*. **14** (2): 214–7. [doi](/source/Doi_(identifier)):[10.1038/ng1096-214](https://doi.org/10.1038%2Fng1096-214). [PMID](/source/PMID_(identifier)) [8841199](https://pubmed.ncbi.nlm.nih.gov/8841199). [S2CID](/source/S2CID_(identifier)) [9712904](https://api.semanticscholar.org/CorpusID:9712904).

- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". *Gene*. **200** (1–2): 149–56. [doi](/source/Doi_(identifier)):[10.1016/S0378-1119(97)00411-3](https://doi.org/10.1016%2FS0378-1119%2897%2900411-3). [PMID](/source/PMID_(identifier)) [9373149](https://pubmed.ncbi.nlm.nih.gov/9373149).

- Zhou D, Salnikow K, Costa M (May 1998). "Cap43, a novel gene specifically induced by Ni2+ compounds". *Cancer Research*. **58** (10): 2182–9. [PMID](/source/PMID_(identifier)) [9605764](https://pubmed.ncbi.nlm.nih.gov/9605764).

- Kurdistani SK, Arizti P, Reimer CL, Sugrue MM, Aaronson SA, Lee SW (October 1998). "Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage". *Cancer Research*. **58** (19): 4439–44. [PMID](/source/PMID_(identifier)) [9766676](https://pubmed.ncbi.nlm.nih.gov/9766676).

- Piquemal D, Joulia D, Balaguer P, Basset A, Marti J, Commes T (July 1999). ["Differential expression of the RTP/Drg1/Ndr1 gene product in proliferating and growth arrested cells"](https://doi.org/10.1016%2FS0167-4889%2899%2900056-7). *Biochimica et Biophysica Acta (BBA) - Molecular Cell Research*. **1450** (3): 364–73. [doi](/source/Doi_(identifier)):[10.1016/S0167-4889(99)00056-7](https://doi.org/10.1016%2FS0167-4889%2899%2900056-7). [PMID](/source/PMID_(identifier)) [10395947](https://pubmed.ncbi.nlm.nih.gov/10395947).

- Guan RJ, Ford HL, Fu Y, Li Y, Shaw LM, Pardee AB (February 2000). "Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer". *Cancer Research*. **60** (3): 749–55. [PMID](/source/PMID_(identifier)) [10676663](https://pubmed.ncbi.nlm.nih.gov/10676663).

- Kalaydjieva L, Gresham D, Gooding R, Heather L, Baas F, de Jonge R, et al. (July 2000). ["N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1287101). *American Journal of Human Genetics*. **67** (1): 47–58. [Bibcode](/source/Bibcode_(identifier)):[2000AmJHG..67...47K](https://ui.adsabs.harvard.edu/abs/2000AmJHG..67...47K). [doi](/source/Doi_(identifier)):[10.1086/302978](https://doi.org/10.1086%2F302978). [PMC](/source/PMC_(identifier)) [1287101](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1287101). [PMID](/source/PMID_(identifier)) [10831399](https://pubmed.ncbi.nlm.nih.gov/10831399).

- Park H, Adams MA, Lachat P, Bosman F, Pang SC, Graham CH (September 2000). "Hypoxia induces the expression of a 43-kDa protein (PROXY-1) in normal and malignant cells". *Biochemical and Biophysical Research Communications*. **276** (1): 321–8. [Bibcode](/source/Bibcode_(identifier)):[2000BBRC..276..321P](https://ui.adsabs.harvard.edu/abs/2000BBRC..276..321P). [doi](/source/Doi_(identifier)):[10.1006/bbrc.2000.3475](https://doi.org/10.1006%2Fbbrc.2000.3475). [PMID](/source/PMID_(identifier)) [11006124](https://pubmed.ncbi.nlm.nih.gov/11006124).

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## External links

- [GeneReviews/NCBI/NIH/UW entry on Charcot-Marie-Tooth Neuropathy Type 4](https://www.ncbi.nlm.nih.gov/books/NBK1468/)

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Adapted from the Wikipedia article [NDRG1](https://en.wikipedia.org/wiki/NDRG1) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/NDRG1?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.