NDRG1

From Wikipedia, the free encyclopedia
  (Redirected from NDRG1 (gene))
Jump to: navigation, search
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 MGI: 1341799 HomoloGene: 55953 GeneCards: NDRG1
Gene location (Human)
Chromosome 8 (human)
Chr. Chromosome 8 (human)[1]
Chromosome 8 (human)
Genomic location for NDRG1
Genomic location for NDRG1
Band 8q24.22 Start 133,237,171 bp[1]
End 133,302,022 bp[1]
RNA expression pattern
PBB GE NDRG1 200632 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001135242
NM_001258432
NM_001258433
NM_006096

NM_008681

RefSeq (protein)

NP_001128714
NP_001245361
NP_001245362
NP_006087

NP_032707

Location (UCSC) Chr 8: 133.24 – 133.3 Mb Chr 8: 66.93 – 66.97 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Protein NDRG1 is a protein that in humans is encoded by the NDRG1 gene.[5][6][7][8]

This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation[citation needed]. 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 effector involved in vesicular recycling.[9]

As reviewed by Fang et al.,[10] NDRG1 is involved in embryogenesis and development, cell growth and differentiation, lipid biosynthesis and myelination, stress responses, immunity, DNA repair and cell adhesion among other functions. NDRG1 is localised in the 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.

Functions in cancer and metastasis[edit]

As reviewed by Kovacevic et al.,[11] NDRG1 is a potent, iron-regulated growth and metastasis suppressor that was found to be negatively correlated with cancer progression in a number of tumors, including prostate, pancreatic, breast, and colon cancers. 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, phosphatidylinositol 3-kinase (PI3K), WNT, 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 and tensin homolog, E-cadherin, and 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[edit]

In one of its functions at a molecular level, NDRG1 binds and stabilizes methyltransferases, chiefly O-6-methylguanine-DNA methyltransferase (MGMT),[12] a DNA repair protein. Thus, higher expression of NDRG1 can promote MGMT protein stability and activity. Dominick et al.[13] 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.

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000104419 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000005125 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ van Belzen N, Dinjens WN, Diesveld MP, Groen NA, van der Made AC, Nozawa Y, Vlietstra R, Trapman J, Bosman FT (Sep 1997). "A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms". Lab Invest. 77 (1): 85–92. PMID 9251681. 
  6. ^ Kokame K, Kato H, Miyata T (Jan 1997). "Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes". J Biol Chem. 271 (47): 29659–65. PMID 8939898. doi:10.1074/jbc.271.47.29659. 
  7. ^ Zhang J, Chen S, Zhang W, Zhang J, Liu X, Shi H, Che H, Wang W, Li F, Yao L (Jun 2008). "Human differentiation-related gene NDRG1 is a Myc downstream-regulated gene that is repressed by Myc on the core promoter region". Gene. 417 (1-2): 5–12. PMID 18455888. doi:10.1016/j.gene.2008.03.002. 
  8. ^ a b "Entrez Gene: NDRG1 N-myc downstream regulated gene 1". 
  9. ^ Kachhap SK, Faith D, Qian DZ, et al. (2007). Heisenberg C, ed. "The N-Myc down regulated Gene1 (NDRG1) Is a Rab4a effector involved in vesicular recycling of E-cadherin". PLoS ONE. 2 (9): e844. PMC 1952073Freely accessible. PMID 17786215. doi:10.1371/journal.pone.0000844.  open access publication – free to read
  10. ^ Fang BA, Kovačević Ž, Park KC, Kalinowski DS, Jansson PJ, Lane DJ, Sahni S, Richardson DR (2014). "Molecular functions of the iron-regulated metastasis suppressor, NDRG1, and its potential as a molecular target for cancer therapy". Biochim. Biophys. Acta. 1845 (1): 1–19. PMID 24269900. doi:10.1016/j.bbcan.2013.11.002. 
  11. ^ Kovacevic Z, Menezes SV, Sahni S, Kalinowski DS, Bae DH, Lane DJ, Richardson DR (2016). "The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways". J. Biol. Chem. 291 (3): 1029–52. PMC 4714189Freely accessible. PMID 26534963. doi:10.1074/jbc.M115.689653. 
  12. ^ Weiler M, Blaes J, Pusch S, Sahm F, Czabanka M, Luger S, Bunse L, Solecki G, Eichwald V, Jugold M, Hodecker S, Osswald M, Meisner C, Hielscher T, Rübmann P, Pfenning PN, Ronellenfitsch M, Kempf T, Schnölzer M, Abdollahi A, Lang F, Bendszus M, von Deimling A, Winkler F, Weller M, Vajkoczy P, Platten M, Wick W (2014). "mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy". Proc. Natl. Acad. Sci. U.S.A. 111 (1): 409–14. PMC 3890826Freely accessible. PMID 24367102. doi:10.1073/pnas.1314469111. 
  13. ^ Dominick G, Bowman J, Li X, Miller RA, Garcia GG (2017). "mTOR regulates the expression of DNA damage response enzymes in long-lived Snell dwarf, GHRKO, and PAPPA-KO mice". Aging Cell. 16 (1): 52–60. PMC 5242303Freely accessible. PMID 27618784. doi:10.1111/acel.12525. 

Further reading[edit]

External links[edit]