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Gene Review

Nrf1  -  nuclear respiratory factor 1

Mus musculus

Synonyms: Alpha palindromic-binding protein, Alpha-pal, C87038, D6Ertd415e, NRF-1, ...
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Disease relevance of Nrf1

  • Hypoxia led to a decline of Nrf1 and 16S rRNA levels also through a mechanism blocked with PK11195 [1].
  • We report here that mice with somatic inactivation of nrf1 in the liver developed hepatic cancer [2].

High impact information on Nrf1

  • The consensus binding sequence (T/C)GCGCA(C/T)GCGC(A/G) of NRF-1 includes a noncanonical CA(C/T)GCG Myc:MAX binding site [3].
  • In this study, we establish a link between the induction of NRF-1 target genes and sensitization to apoptosis on serum depletion [3].
  • Cytochrome c and other nuclear-encoded mitochondrial genes are regulated by the transcription factor nuclear respiratory factor-1 (NRF-1) [3].
  • The cDNA-encoded protein was indistinguishable from the authentic HeLa cell factor on denaturing gels, displayed the expected NRF-1 DNA-binding specificity, and made the same guanine nucleotide contacts as HeLa NRF-1 on binding known NRF-1 recognition sites [4].
  • In addition, hepatocytes lacking Nrf1 showed oxidative stress, and gene expression analysis showed decreased expression of various ARE-containing genes, and up-regulation of CYP4A genes [2].

Biological context of Nrf1


Anatomical context of Nrf1

  • In fully differentiated odontoblasts, the loss of interaction between Nrf1 and C/EBPbeta results in an increased DSPP transcription [5].
  • The expression of Ppargc1a and Nrf1 was also stimulated by n-3 polyunsaturated fatty acids in 3T3-L1 cells [8].
  • We show by chimera analysis that Nrf1 is essential for the hepatocyte lineage [6].
  • Mouse embryonic stem cells lacking Nrf1 developed normally and contributed to most tissues in adult chimeras where Nrf1 is normally expressed [6].
  • Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal transmembrane domain. Inhibition of nuclear translocation and transacting function [9].

Associations of Nrf1 with chemical compounds

  • In addition, cells deficient in Nrf1 were sensitized to the cytotoxic effects of tumor necrosis factor (TNF) [6].
  • Our results indicate that Nrf1 plays a role in the regulation of genes involved in glutathione synthesis and suggest a basis for a correspondingly low GSH concentration and reduced stress response [10].
  • Treatment with tunicamycin, an endoplasmic reticulum stress inducer, caused an accumulation of a smaller form of Nrf1 that correlated with detection of Nrf1 in the nucleus by biochemical fractionation and immunofluorescent analysis [9].
  • A novel splice variant of Nrf1 with a 411 bp deletion of the serine-rich region, resulting in an overall structure reminiscent of the BTB and CNC homology (Bach) proteins, was isolated from the corresponding DC18 cells [11].
  • Interestingly, a fraction of the blastocysts from heterozygous matings had reduced staining intensity with rhodamine 123 and NRF-1(-/-) blastocysts had markedly reduced levels of mitochondrial DNA (mtDNA) [12].

Regulatory relationships of Nrf1

  • In undifferentiated odontoblasts, Nrf1 and C/EBPbeta repress DSPP promoter activity individually and synergistically by cooperatively interacting with each other [5].

Other interactions of Nrf1


Analytical, diagnostic and therapeutic context of Nrf1


  1. Mitochondrial benzodiazepine receptors regulate oxygen homeostasis in the early mouse embryo. O'Hara, M.F., Nibbio, B.J., Craig, R.C., Nemeth, K.R., Charlap, J.H., Knudsen, T.B. Reprod. Toxicol. (2003) [Pubmed]
  2. Liver-specific inactivation of the Nrf1 gene in adult mouse leads to nonalcoholic steatohepatitis and hepatic neoplasia. Xu, Z., Chen, L., Leung, L., Yen, T.S., Lee, C., Chan, J.Y. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. c-MYC apoptotic function is mediated by NRF-1 target genes. Morrish, F., Giedt, C., Hockenbery, D. Genes Dev. (2003) [Pubmed]
  4. NRF-1, an activator involved in nuclear-mitochondrial interactions, utilizes a new DNA-binding domain conserved in a family of developmental regulators. Virbasius, C.A., Virbasius, J.V., Scarpulla, R.C. Genes Dev. (1993) [Pubmed]
  5. The CCAAT enhancer-binding protein (C/EBP)beta and Nrf1 interact to regulate dentin sialophosphoprotein (DSPP) gene expression during odontoblast differentiation. Narayanan, K., Ramachandran, A., Peterson, M.C., Hao, J., Kolstø, A.B., Friedman, A.D., George, A. J. Biol. Chem. (2004) [Pubmed]
  6. Nrf1 is critical for redox balance and survival of liver cells during development. Chen, L., Kwong, M., Lu, R., Ginzinger, D., Lee, C., Leung, L., Chan, J.Y. Mol. Cell. Biol. (2003) [Pubmed]
  7. Coding sequence, chromosomal localization, and expression pattern of Nrf1: the mouse homolog of Drosophila erect wing. Schaefer, L., Engman, H., Miller, J.B. Mamm. Genome (2000) [Pubmed]
  8. Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Flachs, P., Horakova, O., Brauner, P., Rossmeisl, M., Pecina, P., Franssen-van Hal, N., Ruzickova, J., Sponarova, J., Drahota, Z., Vlcek, C., Keijer, J., Houstek, J., Kopecky, J. Diabetologia (2005) [Pubmed]
  9. Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal transmembrane domain. Inhibition of nuclear translocation and transacting function. Wang, W., Chan, J.Y. J. Biol. Chem. (2006) [Pubmed]
  10. The CNC basic leucine zipper factor, Nrf1, is essential for cell survival in response to oxidative stress-inducing agents. Role for Nrf1 in gamma-gcs(l) and gss expression in mouse fibroblasts. Kwong, M., Kan, Y.W., Chan, J.Y. J. Biol. Chem. (1999) [Pubmed]
  11. A novel splice variant of the transcription factor Nrf1 interacts with the TNFalpha promoter and stimulates transcription. Prieschl, E.E., Novotny, V., Csonga, R., Jaksche, D., Elbe-Bürger, A., Thumb, W., Auer, M., Stingl, G., Baumruker, T. Nucleic Acids Res. (1998) [Pubmed]
  12. Mitochondrial DNA instability and peri-implantation lethality associated with targeted disruption of nuclear respiratory factor 1 in mice. Huo, L., Scarpulla, R.C. Mol. Cell. Biol. (2001) [Pubmed]
  13. Mitochondrial biogenesis in brown adipose tissue is associated with differential expression of transcription regulatory factors. Villena, J.A., Carmona, M.C., Rodriguez de la Concepción, M., Rossmeisl, M., Viñas, O., Mampel, T., Iglesias, R., Giralt, M., Villarroya, F. Cell. Mol. Life Sci. (2002) [Pubmed]
  14. Identification of a nuclear respiratory factor-1 binding site within the core promoter of the human polio virus receptor/CD155 gene. Solecki, D., Bernhardt, G., Lipp, M., Wimmer, E. J. Biol. Chem. (2000) [Pubmed]
  15. Characterization and identification of promoter elements in the mouse COX17 gene. Takahashi, Y., Kako, K., Arai, H., Ohishi, T., Inada, Y., Takehara, A., Fukamizu, A., Munekata, E. Biochim. Biophys. Acta (2002) [Pubmed]
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