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Gene Review

NBR2  -  neighbor of BRCA1 gene 2 (non-protein coding)

Homo sapiens

Synonyms: NCRNA00192, Neighbor of BRCA1 gene 2 protein, Next to BRCA1 gene 2 protein
 
 

  

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Disease relevance of NBR2

  • Single-strand conformation polymorphism (SSCP) analysis of the NBR2 gene failed to identify any mutations in either breast or ovarian cancer, suggesting that if the NBR2 gene is involved in the development of these cancers, other mechanisms for tumorigenesis may exist [1].
  • The expression of NBR2 differed, being increased in three permanent tumour cell lines and slightly decreased in all primary breast cancer cell cultures [2].
 

High impact information on NBR2

  • Isolation and characterisation of the NBR2 gene which lies head to head with the human BRCA1 gene [1].
  • The NBR2 gene contains five exons spanning a genomic region of approximately 30 kb between the BRCA1 and pseudo-BRCA1 genes [1].
  • The NBR2 cDNA contains an open reading frame of 112 amino acids and is predicted to encode a protein of approximately 12 kDa [1].
  • Deletion analyses further delineated a minimal 56-bp EcoRI-HaeIII fragment, which could drive transcription in the NBR2 gene direction 2-4-fold higher than in the BRCA1 direction in all cell lines tested [3].
  • In MBD2 knockdown cells, transient expression of a Mbd2 cDNA, refractory to siRNA-mediated decay, shifted down the NBR2 mRNA level to that observed in unmodified HeLa cells [4].
 

Biological context of NBR2

  • The physical distance between the transcription start sites of the NBR2 and BRCA1 genes is 218 bp, suggesting that regulation of the expression of both genes may be co-ordinated through a bi-directional promoter [1].
  • Analysis of multiple reporter gene constructs containing the BRCA1 genomic region driving transcription in both directions suggests that the putative negative regulatory element functions to block transcription only in the BRCA1 direction, although the promoter is shared by the divergently transcribed NBR2 gene [5].
  • Specific binding of the methyl binding domain protein 2 at the BRCA1-NBR2 locus [4].
  • The human BRCA1 and NBR2 genes and the homologous Brcal and Nbr1 mouse genes are situated head-to-head on human chromosome 17q21 and on mouse chromosome 11, respectively [2].
  • NBR2 recently was identified as a glucose starvation-induced long non-coding RNA [6]. NBR2 interacts with AMP-activated protein kinase (AMPK) [7], a critical energy sensor in most eukaryotic cells, and promotes AMPK function to mediate energy stress response. Knockdown of NBR2 attenuates energy stress-induced AMPK activation, resulting in unchecked cell cycling, altered apoptosis/autophagy response, and increased tumour development in vivo  [8] [9]  . It is now appreciated that NBR2, a former junk gene, plays critical roles in tumor suppression   
 

Anatomical context of NBR2

  • Furthermore, transcriptional activity in the BRCA1 direction was undetectable in the muscle cell line C2C12, whereas activity in the NBR2 direction was maintained [3].
 

Other interactions of NBR2

References

  1. Isolation and characterisation of the NBR2 gene which lies head to head with the human BRCA1 gene. Xu, C.F., Brown, M.A., Nicolai, H., Chambers, J.A., Griffiths, B.L., Solomon, E. Hum. Mol. Genet. (1997) [Pubmed]
  2. Expression of BRCA1, NBR1 and NBR2 genes in human breast cancer cells. Dimitrov, S.D., Matousková, E., Forejt, J. Folia Biol. (Praha) (2001) [Pubmed]
  3. Transcription of BRCA1 is dependent on the formation of a specific protein-DNA complex on the minimal BRCA1 Bi-directional promoter. Suen, T.C., Goss, P.E. J. Biol. Chem. (1999) [Pubmed]
  4. Specific binding of the methyl binding domain protein 2 at the BRCA1-NBR2 locus. Auriol, E., Billard, L.M., Magdinier, F., Dante, R. Nucleic Acids Res. (2005) [Pubmed]
  5. Identification of a novel transcriptional repressor element located in the first intron of the human BRCA1 gene. Suen, T.C., Goss, P.E. Oncogene (2001) [Pubmed]
  6. lincRNAs: genomics, evolution, and mechanisms. Ulitsky, I., Bartel, D.P. Cell. (2013) [Pubmed]
  7. AMPK: An Energy-Sensing Pathway with Multiple Inputs and Outputs. Hardie, D.G., Schaffer, B.E., Brunet, A. Trends. Cell. Biol. (2016) [Pubmed]
  8. LncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress. Liu, X., Xiao, Z.D., Han, L., Zhang, J., Lee, S.W., Wang, W., Lee, H., Zhuang, L., Chen, J., Lin, H.K., Wang, J., Liang, H., Gan, B. Nat. Cell. Biol. (2016) [Pubmed]
  9. An lncRNA switch for AMPK activation. Liu, X., Xiao, Z.D., Gan, B. Cell. Cycle. (2016) [Pubmed]
 
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