Biology:NRF1

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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.

Function

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.

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.

Cyclin D1-dependent kinase, through phosphorylating NRF-1 at S47, coordinates nuclear DNA synthesis and mitochondrial function.

Interactions

NRF1 has been shown to interact with DYNLL1, PPARGC1A, and PPRC1.

Further reading

• "The gene (NFE2L1) for human NRF-1, an activator involved in nuclear-mitochondrial interactions, maps to 7q32". Genomics 27 (3): 555–7. 1995. doi:10.1006/geno.1995.1094. PMID 7558044. 
• "Structure, expression, and chromosomal assignment of the human gene encoding nuclear respiratory factor 1". J. Biol. Chem. 270 (30): 18019–25. 1995. doi:10.1074/jbc.270.30.18019. PMID 7629110. 
• "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. 1994. doi:10.1016/S0021-9258(17)32255-X. PMID 8034649. 
• "Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis". Proc. Natl. Acad. Sci. U.S.A. 91 (4): 1309–13. 1994. doi:10.1073/pnas.91.4.1309. PMID 8108407. Bibcode: 1994PNAS...91.1309V. 
• "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. 1994. doi:10.1101/gad.7.12a.2431. PMID 8253388. 
• "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. 1996. doi:10.1093/hmg/4.9.1591. PMID 8541844. 
• "Small Maf proteins interact with the human transcription factor TCF11/Nrf1/LCR-F1". Nucleic Acids Res. 24 (21): 4289–97. 1996. doi:10.1093/nar/24.21.4289. PMID 8932385. 
• "Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14960–5. 1997. doi:10.1073/pnas.93.25.14960. PMID 8962164. Bibcode: 1996PNAS...9314960V. 
• "Role of NRF-1 in bidirectional transcription of the human GPAT-AIRC purine biosynthesis locus". Nucleic Acids Res. 25 (9): 1809–16. 1997. doi:10.1093/nar/25.9.1809. PMID 9108165. 
• "Human small Maf proteins form heterodimers with CNC family transcription factors and recognize the NF-E2 motif". Oncogene 14 (16): 1901–10. 1997. doi:10.1038/sj.onc.1201024. PMID 9150357. 
• "hMAF, a small human transcription factor that heterodimerizes specifically with Nrf1 and Nrf2". J. Biol. Chem. 272 (26): 16490–7. 1997. doi:10.1074/jbc.272.26.16490. PMID 9195958. 
• "Serine phosphorylation within a concise amino-terminal domain in nuclear respiratory factor 1 enhances DNA binding". J. Biol. Chem. 272 (30): 18732–9. 1997. doi:10.1074/jbc.272.30.18732. PMID 9228045. 
• "Interaction of the CNC-bZIP factor TCF11/LCR-F1/Nrf1 with MafG: binding-site selection and regulation of transcription". Nucleic Acids Res. 26 (2): 512–20. 1998. doi:10.1093/nar/26.2.512. PMID 9421508. 
• "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. 1998. doi:10.1046/j.1432-1327.1998.2510164.x. PMID 9492280. 
• "Oxidative stress and upregulation of mitochondrial biogenesis genes in mitochondrial DNA-depleted HeLa cells". Biochem. Biophys. Res. Commun. 258 (1): 44–9. 1999. doi:10.1006/bbrc.1999.0580. PMID 10222232. 
• "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. 1999. doi:10.1074/jbc.274.25.17534. PMID 10364186. 
• "Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1". Cell 98 (1): 115–24. 1999. doi:10.1016/S0092-8674(00)80611-X. PMID 10412986. 
• "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. 2000. doi:10.1074/jbc.275.17.12453. PMID 10777530. 
• "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. 2001. doi:10.1074/jbc.M009629200. PMID 11058604. 

External links

• NRF1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook Nrf1

This article incorporates text from the United States National Library of Medicine, which is in the public domain.