Nuclear respiratory factor 1, also known asNrf1,Nrf-1,NRF1 andNRF-1, encodes a protein thathomodimerizes and functions as atranscription factor which activates the expression of some keymetabolic genes regulating cellular growth and nuclear genes required for respiration,heme biosynthesis, andmitochondrial DNA transcription and replication. The protein has also been associated with the regulation ofneurite outgrowth. Alternatetranscriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different proteinisoforms 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 ofNFE2L1.[citation needed]
Nrf1 functions as a transcription factor that activates the expression of some key metabolic genes regulatingcellular growth and nuclear genes required for mitochondrial respiration, andmitochondrial DNAtranscription andreplication. Nrf1, together withNrf2, mediates thebiogenomic coordination between nuclear and mitochondrial genomes by directly regulating the expression of several nuclear-encodedETC proteins, and indirectly regulating the three mitochondrial-encodedCOX subunit genes by activatingmtTFA,mtTFB1, andmtTFB2.
Nrf1 is associated with the regulation ofneurite outgrowth.[5]
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.[6]
Cyclin D1-dependent kinase, through phosphorylating NRF-1 at S47, coordinates nuclear DNA synthesis and mitochondrial function.[7]
^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.doi:10.1242/jcs.113.23.4263.PMID11069771.
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.
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.
