Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor (erythroid-derived 2)-like 1" which has an official symbol of NFE2L1.[citation needed]
Nrf1 functions as a transcription factor that activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for mitochondrial respiration, and mitochondrial DNA transcription and replication. Nrf1, together with Nrf2, mediates the biogenomic coordination between nuclear and mitochondrial genomes by directly regulating the expression of several nuclear-encoded ETC proteins, and indirectly regulating the three mitochondrial-encoded COX subunit genes by activating mtTFA, mtTFB1, and mtTFB2.
Nrf1 is associated with the regulation of neurite outgrowth.[1]
Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized.[2]
Cyclin D1-dependent kinase, through phosphorylating NRF-1 at S47, coordinates nuclear DNA synthesis and mitochondrial function.[3]
↑Herzig RP, Andersson U, Scarpulla RC (December 2000). "Dynein light chain interacts with NRF-1 and EWG, structurally and functionally related transcription factors from humans and drosophila". J. Cell Sci. 113 (23): 4263–73. PMID11069771.
↑Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (July 1999). "Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1". Cell. 98 (1): 115–24. doi:10.1016/S0092-8674(00)80611-X. PMID10412986.
Tiranti V, Rossi E, Rocchi M, DiDonato S, Zuffardi O, Zeviani M (1995). "The gene (NFE2L1) for human NRF-1, an activator involved in nuclear-mitochondrial interactions, maps to 7q32". Genomics. 27 (3): 555–7. doi:10.1006/geno.1995.1094. PMID7558044.
Gopalakrishnan L, Scarpulla RC (1995). "Structure, expression, and chromosomal assignment of the human gene encoding nuclear respiratory factor 1". J. Biol. Chem. 270 (30): 18019–25. doi:10.1074/jbc.270.30.18019. PMID7629110.
Efiok BJ, Chiorini JA, Safer B (1994). "A key transcription factor for eukaryotic initiation factor-2 alpha is strongly homologous to developmental transcription factors and may link metabolic genes to cellular growth and development". J. Biol. Chem. 269 (29): 18921–30. PMID8034649.
Virbasius CA, Virbasius JV, Scarpulla RC (1994). "NRF-1, an activator involved in nuclear-mitochondrial interactions, utilizes a new DNA-binding domain conserved in a family of developmental regulators". Genes Dev. 7 (12A): 2431–45. doi:10.1101/gad.7.12a.2431. PMID8253388.
Spelbrink JN, Van den Bogert C (1996). "The pre-mRNA of nuclear respiratory factor 1, a regulator of mitochondrial biogenesis, is alternatively spliced in human tissues and cell lines". Hum. Mol. Genet. 4 (9): 1591–6. doi:10.1093/hmg/4.9.1591. PMID8541844.
Toki T, Itoh J, Kitazawa J, Arai K, Hatakeyama K, Akasaka J, Igarashi K, Nomura N, Yokoyama M, Yamamoto M, Ito E (1997). "Human small Maf proteins form heterodimers with CNC family transcription factors and recognize the NF-E2 motif". Oncogene. 14 (16): 1901–10. doi:10.1038/sj.onc.1201024. PMID9150357.
Marini MG, Chan K, Casula L, Kan YW, Cao A, Moi P (1997). "hMAF, a small human transcription factor that heterodimerizes specifically with Nrf1 and Nrf2". J. Biol. Chem. 272 (26): 16490–7. doi:10.1074/jbc.272.26.16490. PMID9195958.
Gugneja S, Scarpulla RC (1997). "Serine phosphorylation within a concise amino-terminal domain in nuclear respiratory factor 1 enhances DNA binding". J. Biol. Chem. 272 (30): 18732–9. doi:10.1074/jbc.272.30.18732. PMID9228045.
Au HC, Scheffler IE (1998). "Promoter analysis of the human succinate dehydrogenase iron-protein gene--both nuclear respiratory factors NRF-1 and NRF-2 are required". Eur. J. Biochem. 251 (1–2): 164–74. doi:10.1046/j.1432-1327.1998.2510164.x. PMID9492280.
Miranda S, Foncea R, Guerrero J, Leighton F (1999). "Oxidative stress and upregulation of mitochondrial biogenesis genes in mitochondrial DNA-depleted HeLa cells". Biochem. Biophys. Res. Commun. 258 (1): 44–9. doi:10.1006/bbrc.1999.0580. PMID10222232.
Li B, Holloszy JO, Semenkovich CF (1999). "Respiratory uncoupling induces delta-aminolevulinate synthase expression through a nuclear respiratory factor-1-dependent mechanism in HeLa cells". J. Biol. Chem. 274 (25): 17534–40. doi:10.1074/jbc.274.25.17534. PMID10364186.
Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999). "Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1". Cell. 98 (1): 115–24. doi:10.1016/S0092-8674(00)80611-X. PMID10412986.
Solecki D, Bernhardt G, Lipp M, Wimmer E (2000). "Identification of a nuclear respiratory factor-1 binding site within the core promoter of the human polio virus receptor/CD155 gene". J. Biol. Chem. 275 (17): 12453–62. doi:10.1074/jbc.275.17.12453. PMID10777530.
Kumari D, Usdin K (2001). "Interaction of the transcription factors USF1, USF2, and alpha -Pal/Nrf-1 with the FMR1 promoter. Implications for Fragile X mental retardation syndrome". J. Biol. Chem. 276 (6): 4357–64. doi:10.1074/jbc.M009629200. PMID11058604.