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Gene Review

NRF1  -  nuclear respiratory factor 1

Homo sapiens

Synonyms: ALPHA-PAL, Alpha palindromic-binding protein, Alpha-pal, EWG, NRF-1, ...
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Disease relevance of NRF1


High impact information on NRF1


Biological context of NRF1


Anatomical context of NRF1

  • Furthermore, overexpression of full-length alpha-Pal/NRF-1 significantly enhanced IAP promoter activity while overexpression of dominant-negative mutant reduced promoter activity both in the cultured human cell lines and primary mouse cortical cells [10].
  • We have reported that overexpression of nuclear respiratory factor-1 (NRF-1) and high concentration (50 mM) of glucose increased the promoter activity of the rat Tfam in L6 rat skeletal muscle cells [13].
  • Respiratory uncoupling induces delta-aminolevulinate synthase expression through a nuclear respiratory factor-1-dependent mechanism in HeLa cells [14].
  • A novel function of transcription factor alpha-Pal/NRF-1: increasing neurite outgrowth [2].
  • Among these is the recognition sequence for a nuclear factor designated NRF-1 (nuclear respiratory factor 1) also found in the upstream regions of several other nuclear genes whose products function in the mitochondria [15].

Associations of NRF1 with chemical compounds

  • It was concluded that high glucose-induced Tfam transcription in L6 cells might be mediated by NRF-1 [13].
  • Role of NRF-1 in bidirectional transcription of the human GPAT-AIRC purine biosynthesis locus [16].
  • In addition, metformin and AICAR increased the mRNA expression of nuclear respiratory factor-1 and mitochondrial DNA transcription factor A (mtTFA) and stimulated the mitochondrial proliferation [17].
  • Thus 17beta-estradiol seemed to exert a dual effect, activating the PI3K-Akt pathway by inhibiting pten mRNA expression and also inhibiting nrf1 and tfam mRNA expression [18].
  • However, only genistein led to increases in the cytosolic accumulation and nuclear translocation of Nrf1 and the increased expression of and activity of glutathione peroxidase [19].

Physical interactions of NRF1


Regulatory relationships of NRF1


Other interactions of NRF1


Analytical, diagnostic and therapeutic context of NRF1


  1. Nuclear respiratory factor 1 plays an essential role in transcriptional initiation from the hepatitis B virus x gene promoter. Tokusumi, Y., Zhou, S., Takada, S. J. Virol. (2004) [Pubmed]
  2. A novel function of transcription factor alpha-Pal/NRF-1: increasing neurite outgrowth. Chang, W.T., Chen, H.I., Chiou, R.J., Chen, C.Y., Huang, A.M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  3. Association between polymorphisms in the nuclear respiratory factor 1 gene and type 2 diabetes mellitus in the Korean population. Cho, Y.M., Shin, H.D., Park, B.L., Kim, J.H., Park, K.S., Kim, S.Y., Lee, H.K. Diabetologia (2005) [Pubmed]
  4. Gene expression in humans with diabetes and prediabetes: what have we learned about diabetes pathophysiology? Patti, M.E. Current opinion in clinical nutrition and metabolic care. (2004) [Pubmed]
  5. Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function. Wang, C., Li, Z., Lu, Y., Du, R., Katiyar, S., Yang, J., Fu, M., Leader, J.E., Quong, A., Novikoff, P.M., Pestell, R.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Patti, M.E., Butte, A.J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., Landaker, E.J., Goldfine, A.B., Mun, E., DeFronzo, R., Finlayson, J., Kahn, C.R., Mandarino, L.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  7. In vivo protein-DNA interactions at human DNA replication origin. Dimitrova, D.S., Giacca, M., Demarchi, F., Biamonti, G., Riva, S., Falaschi, A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. PGC-1-Related Coactivator: Immediate Early Expression and Characterization of a CREB/NRF-1 Binding Domain Associated with Cytochrome c Promoter Occupancy and Respiratory Growth. Vercauteren, K., Pasko, R.A., Gleyzer, N., Marino, V.M., Scarpulla, R.C. Mol. Cell. Biol. (2006) [Pubmed]
  9. Regulation and co-ordination of nuclear gene expression during mitochondrial biogenesis. Goffart, S., Wiesner, R.J. Exp. Physiol. (2003) [Pubmed]
  10. Alpha-Pal/NRF-1 regulates the promoter of the human integrin-associated protein/CD47 gene. Chang, W.T., Huang, A.M. J. Biol. Chem. (2004) [Pubmed]
  11. The pre-mRNA of nuclear respiratory factor 1, a regulator of mitochondrial biogenesis, is alternatively spliced in human tissues and cell lines. Spelbrink, J.N., Van den Bogert, C. Hum. Mol. Genet. (1995) [Pubmed]
  12. Serine phosphorylation within a concise amino-terminal domain in nuclear respiratory factor 1 enhances DNA binding. Gugneja, S., Scarpulla, R.C. J. Biol. Chem. (1997) [Pubmed]
  13. Regulation of mitochondrial transcription factor A expression by high glucose. Choi, Y.S., Lee, K.U., Pak, Y.K. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  14. Respiratory uncoupling induces delta-aminolevulinate synthase expression through a nuclear respiratory factor-1-dependent mechanism in HeLa cells. Li, B., Holloszy, J.O., Semenkovich, C.F. J. Biol. Chem. (1999) [Pubmed]
  15. Interaction of nuclear factors with multiple sites in the somatic cytochrome c promoter. Characterization of upstream NRF-1, ATF, and intron Sp1 recognition sequences. Evans, M.J., Scarpulla, R.C. J. Biol. Chem. (1989) [Pubmed]
  16. Role of NRF-1 in bidirectional transcription of the human GPAT-AIRC purine biosynthesis locus. Chen, S., Nagy, P.L., Zalkin, H. Nucleic Acids Res. (1997) [Pubmed]
  17. Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells. Kukidome, D., Nishikawa, T., Sonoda, K., Imoto, K., Fujisawa, K., Yano, M., Motoshima, H., Taguchi, T., Matsumura, T., Araki, E. Diabetes (2006) [Pubmed]
  18. Expression of mitochondrial biogenesis-signaling factors in brown adipocytes is influenced specifically by 17beta-estradiol, testosterone, and progesterone. Rodr??guez-Cuenca, S., Monjo, M., Gianotti, M., Proenza, A.M., Roca, P. Am. J. Physiol. Endocrinol. Metab. (2007) [Pubmed]
  19. Activation of glutathione peroxidase via Nrf1 mediates genistein's protection against oxidative endothelial cell injury. Hernandez-Montes, E., Pollard, S.E., Vauzour, D., Jofre-Montseny, L., Rota, C., Rimbach, G., Weinberg, P.D., Spencer, J.P. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  20. In vitro methylation of nuclear respiratory factor-1 binding site suppresses the promoter activity of mitochondrial transcription factor A. Choi, Y.S., Kim, S., Kyu Lee, H., Lee, K.U., Pak, Y.K. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  21. Effect of four genes (ALDH1, NRF1, JAM and KBL) on proliferation arrest in a non-small cell bronchopulmonary cancer line. Jacquot, C., Lanco, X., Carbonnelle, D., Sevestre, O., Tomasoni, C., Briad, G., Juget, M., Roussis, V., Roussakis, C. Anticancer Res. (2002) [Pubmed]
  22. Increased expression of mitochondrial transcription factor A and nuclear respiratory factor-1 in skeletal muscle from aged human subjects. Lezza, A.M., Pesce, V., Cormio, A., Fracasso, F., Vecchiet, J., Felzani, G., Cantatore, P., Gadaleta, M.N. FEBS Lett. (2001) [Pubmed]
  23. Plasticity of skeletal muscle mitochondria: structure and function. Hoppeler, H., Fluck, M. Medicine and science in sports and exercise. (2003) [Pubmed]
  24. Phylogenetic footprinting of the human cytochrome c oxidase subunit VB promoter. Bachman, N.J., Yang, T.L., Dasen, J.S., Ernst, R.E., Lomax, M.I. Arch. Biochem. Biophys. (1996) [Pubmed]
  25. NHE-1 inhibition improves cardiac mitochondrial function through regulation of mitochondrial biogenesis during postinfarction remodeling. Javadov, S., Purdham, D.M., Zeidan, A., Karmazyn, M. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  26. Structural and functional characterization of the human FMR1 promoter reveals similarities with the hnRNP-A2 promoter region. Drouin, R., Angers, M., Dallaire, N., Rose, T.M., Khandjian, E.W., Rousseau, F. Hum. Mol. Genet. (1997) [Pubmed]
  27. Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. Pilegaard, H., Saltin, B., Neufer, P.D. J. Physiol. (Lond.) (2003) [Pubmed]
  28. Negative regulation of the Nrf1 transcription factor by its N-terminal domain is independent of Keap1: Nrf1, but not Nrf2, is targeted to the endoplasmic reticulum. Zhang, Y., Crouch, D.H., Yamamoto, M., Hayes, J.D. Biochem. J. (2006) [Pubmed]
  29. Characterization of cis- and trans-acting elements in the imprinted human SNURF-SNRPN locus. Rodriguez-Jato, S., Nicholls, R.D., Driscoll, D.J., Yang, T.P. Nucleic Acids Res. (2005) [Pubmed]
  30. Activity-dependent transcriptional regulation of nuclear respiratory factor-1 in cultured rat visual cortical neurons. Yang, S.J., Liang, H.L., Wong-Riley, M.T. Neuroscience (2006) [Pubmed]
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