NRF1

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{{Hatnote|Not to be confused with nuclear factor (erythroid-derived 2)-like 1 or NFE2L1.

Nuclear respiratory factor 1
Identifiers
Symbols NRF1 ; ALPHA-PAL
External IDs OMIM600879 MGI1332235 HomoloGene3674 GeneCards: NRF1 Gene
RNA expression pattern
PBB GE NRF1 204651 at tn.png
PBB GE NRF1 204652 s at tn.png
PBB GE NRF1 211279 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4899 18181
Ensembl ENSG00000106459 ENSMUSG00000058440
UniProt Q16656 Q9WU00
RefSeq (mRNA) NM_001040110 NM_001164226
RefSeq (protein) NP_001035199 NP_001157698
Location (UCSC) Chr 7:
129.25 – 129.4 Mb
Chr 6:
30.05 – 30.15 Mb
PubMed search [1] [2]

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. [provided by RefSeq]

Function[edit]

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. The Nrf proteins are also important for the upregulation of antioxidant and xenobiotic-metabolizing enzymes during oxidative stress.[1]

Nrf1 is also involved in heme biosynthesis through regulation of globin gene expression.[2] The protein has also been associated with the regulation of neurite outgrowth.[3]

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.[4]

Cyclin D1-dependent kinase, through phosphorylating NRF-1 at S47, coordinates nuclear DNA synthesis and mitochondrial function.[5]

Interactions[edit]

Nrf1 heterodimerizes with small Maf proteins and the resultant heterodimers bind to the antioxidant response element (ARE) thereby mediating the transcription of antioxidative and phase 2-metabolizing enzymes.[1][6]

NRF1 has been shown to interact with DYNLL1[7] and PPARGC1A.[8]

References[edit]

  1. ^ a b Biswas M, Chan JY (April 2010). "Role of Nrf1 in antioxidant response element-mediated gene expression and beyond". Toxicol. Appl. Pharmacol. 244 (1): 16–20. doi:10.1016/j.taap.2009.07.034. PMC 2837788. PMID 19665035. 
  2. ^ Chan JY, Han XL, Kan YW (December 1993). "Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast". Proc. Natl. Acad. Sci. U.S.A. 90 (23): 11371–5. doi:10.1073/pnas.90.23.11371. PMC 47984. PMID 8248256. 
  3. ^ Chang WT, Chen HI, Chiou RJ, Chen CY, Huang AM (August 2005). "A novel function of transcription factor alpha-Pal/NRF-1: increasing neurite outgrowth". Biochem. Biophys. Res. Commun. 334 (1): 199–206. doi:10.1016/j.bbrc.2005.06.079. PMID 15992771. 
  4. ^ "Entrez Gene: NRF1 nuclear respiratory factor 1". 
  5. ^ Wang C1, Li Z, Lu Y, Du R, Katiyar S, Yang J, Fu M, Leader JE, Quong A, Novikoff PM, Pestell RG. Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function. Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11567-72. Epub 2006 Jul 24. url = http://www.ncbi.nlm.nih.gov/pubmed/16864783
  6. ^ Wang W, Kwok AM, Chan JY (August 2007). "The p65 isoform of Nrf1 is a dominant negative inhibitor of ARE-mediated transcription". J. Biol. Chem. 282 (34): 24670–8. doi:10.1074/jbc.M700159200. PMID 17609210. 
  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 Pt 23: 4263–73. PMID 11069771. 
  8. ^ 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. PMID 10412986. 

Further reading[edit]

External links[edit]

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