From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
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 ]
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.
[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]
Interactions
NRF1 has been shown to
interact with
DYNLL1 ,
[8]
PPARGC1A ,
[9] and
PPRC1 .
[10]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000106459 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000058440 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ 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 .
^
"Entrez Gene: NRF1 nuclear respiratory factor 1" .
^ Wang C, Li Z, Lu Y, Du R, Katiyar S, Yang J, Fu M, Leader JE, Quong A, Novikoff PM, Pestell RG (2006).
"Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function" . Proceedings of the National Academy of Sciences . 103 (31): 11567–72.
Bibcode :
2006PNAS..10311567W .
doi :
10.1073/pnas.0603363103 .
JSTOR
30051572 .
PMC
1518800 .
PMID
16864783 .
^ 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 .
PMID
11069771 .
^ 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 .
S2CID
16143809 .
^ Andersson U, Scarpulla RC (May 2001).
"PGC-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells" . Mol. Cell. Biol . 21 (11): 3738–49.
doi :
10.1128/MCB.21.11.3738-3749.2001 .
PMC
87014 .
PMID
11340167 .
Further reading
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 .
PMID
7558044 .
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 .
PMID
7629110 .
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.
doi :
10.1016/S0021-9258(17)32255-X .
PMID
8034649 .
Virbasius JV, Scarpulla RC (1994).
"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.
Bibcode :
1994PNAS...91.1309V .
doi :
10.1073/pnas.91.4.1309 .
PMC
43147 .
PMID
8108407 .
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 .
PMID
8253388 .
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 .
PMID
8541844 .
Johnsen O, Skammelsrud N, Luna L, Nishizawa M, Prydz H, Kolstø AB (1996).
"Small Maf proteins interact with the human transcription factor TCF11/Nrf1/LCR-F1" . Nucleic Acids Res . 24 (21): 4289–97.
doi :
10.1093/nar/24.21.4289 .
PMC
146217 .
PMID
8932385 .
Venugopal R, Jaiswal AK (1997).
"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.
Bibcode :
1996PNAS...9314960V .
doi :
10.1073/pnas.93.25.14960 .
PMC
26245 .
PMID
8962164 .
Chen S, Nagy PL, Zalkin H (1997).
"Role of NRF-1 in bidirectional transcription of the human GPAT-AIRC purine biosynthesis locus" . Nucleic Acids Res . 25 (9): 1809–16.
doi :
10.1093/nar/25.9.1809 .
PMC
146651 .
PMID
9108165 .
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 .
PMID
9150357 .
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 .
PMID
9195958 .
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 .
PMID
9228045 .
Johnsen O, Murphy P, Prydz H, Kolsto AB (1998).
"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.
doi :
10.1093/nar/26.2.512 .
PMC
147270 .
PMID
9421508 .
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 .
PMID
9492280 .
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 .
PMID
10222232 .
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 .
PMID
10364186 .
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 .
PMID
10412986 .
S2CID
16143809 .
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 .
PMID
10777530 .
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 .
PMID
11058604 .
External links
This article incorporates text from the
United States National Library of Medicine , which is in the
public domain .
(1) Basic domains
(1.1) Basic
leucine zipper (
bZIP )(1.2) Basic helix-loop-helix (
bHLH )
Group A Group B Group C bHLH-
PAS Group D Group E Group F bHLH-COE
(1.3)
bHLH-ZIP (1.4) NF-1 (1.5) RF-X (1.6) Basic helix-span-helix (bHSH)
(2)
Zinc finger DNA-binding domains
(2.1)
Nuclear receptor (Cys4 )
subfamily 1 subfamily 2 subfamily 3 subfamily 4 subfamily 5 subfamily 6 subfamily 0
(2.2) Other Cys4 (2.3) Cys2 His2 (2.4) Cys6 (2.5) Alternating composition (2.6) WRKY
(4) β-Scaffold factors with minor groove contacts
(0) Other transcription factors