Genomes and Genes
nuclear respiratory factor 1
Summary: A transcription factor that controls the expression of variety of proteins including CYTOCHROME C and 5-AMINOLEVULINATE SYNTHETASE. It plays an important role in maintenance of the RESPIRATORY CHAIN of MITOCHONDRIA.
- Gleyzer N, Vercauteren K, Scarpulla R. Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol. 2005;25:1354-66 pubmed..These results support the conclusion that the coordinate regulation of nucleus-encoded mitochondrial transcription factors by NRFs and PGC-1 family coactivators is essential to the control of mitochondrial biogenesis. ..
- Chan J, Han X, Kan Y. Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proc Natl Acad Sci U S A. 1993;90:11371-5 pubmed..The ubiquitous expression pattern of Nrf1 and the range of promoters containing the NF-E2 binding motif suggest that this gene may play a role in the regulation of heme synthesis and ferritin genes. ..
- Xu Z, Chen L, Leung L, Yen T, Lee C, Chan J. Liver-specific inactivation of the Nrf1 gene in adult mouse leads to nonalcoholic steatohepatitis and hepatic neoplasia. Proc Natl Acad Sci U S A. 2005;102:4120-5 pubmed..Because the phenotype is similar to nonalcoholic steatohepatitis, these animals may prove useful as a model for investigating molecular mechanisms of nonalcoholic steatohepatitis and liver cancer. ..
- Chang W, Chen H, Chiou R, Chen C, Huang A. A novel function of transcription factor alpha-Pal/NRF-1: increasing neurite outgrowth. Biochem Biophys Res Commun. 2005;334:199-206 pubmed..These findings indicate that a novel function of alpha-Pal/NRF-1 is to regulate neuronal differentiation, and that this function is mediated partly via its downstream IAP gene. ..
- Leung L, Kwong M, Hou S, Lee C, Chan J. Deficiency of the Nrf1 and Nrf2 transcription factors results in early embryonic lethality and severe oxidative stress. J Biol Chem. 2003;278:48021-9 pubmed..Together, these findings indicate that the functions of Nrf1 and Nrf2 overlap during early development and to a large extent in regulating antioxidant gene expression in cells. ..
- Short K, Vittone J, Bigelow M, Proctor D, Rizza R, Coenen Schimke J, et al. Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity. Diabetes. 2003;52:1888-96 pubmed..Thus, the muscle mitochondrial response to 4 months of aerobic exercise training was similar in all age-groups, although the older people did not have an improvement in insulin sensitivity. ..
- Patti M, Butte A, Crunkhorn S, Cusi K, Berria R, Kashyap S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A. 2003;100:8466-71 pubmed..Decreased PGC1 expression may be responsible for decreased expression of NRF-dependent genes, leading to the metabolic disturbances characteristic of insulin resistance and DM. ..
- Zhang Y, Lucocq J, Yamamoto M, Hayes J. The NHB1 (N-terminal homology box 1) sequence in transcription factor Nrf1 is required to anchor it to the endoplasmic reticulum and also to enable its asparagine-glycosylation. Biochem J. 2007;408:161-72 pubmed..Wild-type Nrf1 is glycosylated through its Asn/Ser/Thr-rich domain, between amino acids 296 and 403, and this modification was not observed in an Nrf1(Delta299-400) mutant. Glycosylation of Nrf1 was not necessary to retain it in the ER. ..
- Izumi H, Ohta R, Nagatani G, Ise T, Nakayama Y, Nomoto M, et al. p300/CBP-associated factor (P/CAF) interacts with nuclear respiratory factor-1 to regulate the UDP-N-acetyl-alpha-d-galactosamine: polypeptide N-acetylgalactosaminyltransferase-3 gene. Biochem J. 2003;373:713-22 pubmed..Additionally, induced expression of P/CAF may be a component of the adenocarcinoma differentiation process. ..
- Fazio I, Bolger T, Gill G. Conserved regions of the Drosophila erect wing protein contribute both positively and negatively to transcriptional activity. J Biol Chem. 2001;276:18710-6 pubmed..both the activation domain and the inhibitory region are conserved in EWG homologs including human nuclear respiratory factor 1 (NRF-1) and the sea urchin P3A2 protein...
- Ramachandran B, Yu G, Gulick T. Nuclear respiratory factor 1 controls myocyte enhancer factor 2A transcription to provide a mechanism for coordinate expression of respiratory chain subunits. J Biol Chem. 2008;283:11935-46 pubmed publisher..Our findings also account for the previously described indirect regulation by NRF1 of other MEF2 targets in muscle such as GLUT4. ..
- Miyamoto N, Izumi H, Miyamoto R, Kondo H, Tawara A, Sasaguri Y, et al. Quercetin induces the expression of peroxiredoxins 3 and 5 via the Nrf2/NRF1 transcription pathway. Invest Ophthalmol Vis Sci. 2011;52:1055-63 pubmed publisher..Quercetin upregulates the antioxidant peroxiredoxins through the activation of the Nrf2/NRF1 transcription pathway and protects against oxidative stress-induced ocular disease. ..
- Finck B, Kelly D. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) regulatory cascade in cardiac physiology and disease. Circulation. 2007;115:2540-8 pubmed
- Scarpulla R. Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem. 2006;97:673-83 pubmed..This system provides a mechanism for linking respiratory chain expression to environmental conditions and for integrating it with other functions related to cellular energetics. ..
- Liu Y, Niu N, Zhu X, Du T, Wang X, Chen D, et al. Genetic variation and association analyses of the nuclear respiratory factor 1 (nRF1) gene in Chinese patients with type 2 diabetes. Diabetes. 2008;57:777-82 pubmedb>Nuclear respiratory factor 1 (NRF1) is a strong biological and positional candidate to contribute to type 2 diabetes susceptibility...
- Mahishi L, Usdin K. NF-Y, AP2, Nrf1 and Sp1 regulate the fragile X-related gene 2 (FXR2). Biochem J. 2006;400:327-35 pubmed
- Wang C, Li Z, Lu Y, Du R, Katiyar S, Yang J, et al. Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function. Proc Natl Acad Sci U S A. 2006;103:11567-72 pubmed..b>Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by ..
- Wang W, Chan J. Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal transmembrane domain. Inhibition of nuclear translocation and transacting function. J Biol Chem. 2006;281:19676-87 pubmed..These results suggest that Nrf1 is normally targeted to the endoplasmic reticulum membrane and that endoplasmic reticulum stress may play a role in modulating Nrf1 function as a transcriptional activator. ..
- Hossain M, Ji P, Anish R, Jacobson R, Takada S. Poly(ADP-ribose) Polymerase 1 Interacts with Nuclear Respiratory Factor 1 (NRF-1) and Plays a Role in NRF-1 Transcriptional Regulation. J Biol Chem. 2009;284:8621-32 pubmed publisherb>Nuclear respiratory factor 1 (NRF-1) is one of the key transcriptional activators for nuclear-coded genes involved in mitochondrial biogenesis and function as well as for many housekeeping genes...
- Shao D, Liu Y, Liu X, Zhu L, Cui Y, Cui A, et al. PGC-1 beta-regulated mitochondrial biogenesis and function in myotubes is mediated by NRF-1 and ERR alpha. Mitochondrion. 2010;10:516-27 pubmed publisher..Taken together, these results confirm the direct interaction of NRF-1 and ERR alpha with PGC-1 beta, and their participation in mitochondrial biogenesis and respiration. ..
- Gopalakrishnan L, Scarpulla R. Structure, expression, and chromosomal assignment of the human gene encoding nuclear respiratory factor 1. J Biol Chem. 1995;270:18019-25 pubmedb>Nuclear respiratory factor 1 (NRF-1) is a transcription factor that acts on nuclear genes encoding respiratory subunits and components of the mitochondrial transcription and replication machinery...
- Smith K, Coffee B, Reines D. Occupancy and synergistic activation of the FMR1 promoter by Nrf-1 and Sp1 in vivo. Hum Mol Genet. 2004;13:1611-21 pubmed..These findings provide the first direct in vivo evidence identifying the specific transcription factors that regulate FMR1. ..
- Bergeron R, Ren J, Cadman K, Moore I, Perret P, Pypaert M, et al. Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. Am J Physiol Endocrinol Metab. 2001;281:E1340-6 pubmed..Our data suggest that AMPK may play an important role in muscle adaptations to chronic energy stress and that it promotes mitochondrial biogenesis and expression of respiratory proteins through activation of NRF-1...
- Johnsen O, Skammelsrud N, Luna L, Nishizawa M, Prydz H, Kolstø A. Small Maf proteins interact with the human transcription factor TCF11/Nrf1/LCR-F1. Nucleic Acids Res. 1996;24:4289-97 pubmed..These findings place TCF11 as a good candidate for the proposed widely expressed factor(s) known to interact with small Maf proteins and bind NF-E2 sites in a sequence-specific manner resembling NF-E2. ..
- Cho Y, Shin H, Park B, Kim J, Park K, Kim S, et al. Association between polymorphisms in the nuclear respiratory factor 1 gene and type 2 diabetes mellitus in the Korean population. Diabetologia. 2005;48:2033-8 pubmed..b>Nuclear respiratory factor 1 (NRF1) is a transcription factor that acts on nuclear genes encoding respiratory subunits and ..
- Cam H, Balciunaite E, Blais A, Spektor A, Scarpulla R, Young R, et al. A common set of gene regulatory networks links metabolism and growth inhibition. Mol Cell. 2004;16:399-411 pubmed..Our studies provide insights into E2F regulatory circuitry, suggest how factor occupancy can predict the expression signature of a given target gene, and reveal pathways deregulated in human tumors. ..
- Zhang Y, Crouch D, Yamamoto M, Hayes J. Negative regulation of the Nrf1 transcription factor by its N-terminal domain is independent of Keap1: Nrf1, but not Nrf2, is targeted to the endoplasmic reticulum. Biochem J. 2006;399:373-85 pubmed..Thus Nrf1 and Nrf2 are targeted to different subcellular compartments and are negatively regulated by distinct mechanisms. ..
- Baar K, Song Z, Semenkovich C, Jones T, Han D, Nolte L, et al. Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity. FASEB J. 2003;17:1666-73 pubmedb>Nuclear respiratory factor 1 (NRF-1) is a transcriptional activator of nuclear genes that encode a range of mitochondrial proteins including cytochrome c, various other respiratory chain subunits, and delta-aminolevulinate synthase...
- Scarpulla R. Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta. 2002;1576:1-14 pubmed..The interplay of these nuclear factors appears to be a major determinant in regulating the biogenesis of mitochondria. ..
- Biswas M, Phan D, Watanabe M, Chan J. The Fbw7 tumor suppressor regulates nuclear factor E2-related factor 1 transcription factor turnover through proteasome-mediated proteolysis. J Biol Chem. 2011;286:39282-9 pubmed publisher..Together, these data identify Fbw7 as a regulator of Nrf1 expression and reveal a novel function of Fbw7 in cellular stress response...
- Kobayashi A, Tsukide T, Miyasaka T, Morita T, Mizoroki T, Saito Y, et al. Central nervous system-specific deletion of transcription factor Nrf1 causes progressive motor neuronal dysfunction. Genes Cells. 2011;16:692-703 pubmed publisher..These results show that Nrf1 sustains the CNS homeostasis through regulating target genes distinct from those regulated by Nrf2. ..
- Venugopal R, Jaiswal A. 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. 1996;93:14960-5 pubmed..The hARE-mediated basal expression, however, is repressed by overexpression of c-Fos and Fra1. ..
- Zhang Y, Hayes J. Identification of topological determinants in the N-terminal domain of transcription factor Nrf1 that control its orientation in the endoplasmic reticulum membrane. Biochem J. 2010;430:497-510 pubmed publisher..Thus Nrf1 can adopt several topologies within membranes that are determined by its NTD. ..
- Prieschl E, Novotny V, Csonga R, Jaksche D, Elbe Bürger A, Thumb W, et al. A novel splice variant of the transcription factor Nrf1 interacts with the TNFalpha promoter and stimulates transcription. Nucleic Acids Res. 1998;26:2291-7 pubmed..In addition, cotransfection studies demonstrate that this splice variant mediates induced transcription at the TNFalpha promoter after stimulation/activation in a heterologous system. ..
- Dhar S, Liang H, Wong Riley M. Transcriptional coupling of synaptic transmission and energy metabolism: role of nuclear respiratory factor 1 in co-regulating neuronal nitric oxide synthase and cytochrome c oxidase genes in neurons. Biochim Biophys Acta. 2009;1793:1604-13 pubmed publisher..Recently, we found that the same transcription factor, nuclear respiratory factor 1 (NRF-1) co-regulates an important energy-generating enzyme, cytochrome c oxidase, as well as critical ..
- Dhar S, Liang H, Wong Riley M. Nuclear respiratory factor 1 co-regulates AMPA glutamate receptor subunit 2 and cytochrome c oxidase: tight coupling of glutamatergic transmission and energy metabolism in neurons. J Neurochem. 2009;108:1595-606 pubmed publisher..b>Nuclear respiratory factor 1 (NRF-1) was a viable candidate because it regulates all COX subunits and potentially activates Gria2...
- Radhakrishnan S, Lee C, Young P, Beskow A, Chan J, Deshaies R. Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells. Mol Cell. 2010;38:17-28 pubmed publisher..Taken together, our results suggest that Nrf1-mediated proteasome homeostasis could be an attractive target for therapeutic intervention in cancer. ..
- Ivanova M, Luken K, Zimmer A, Lenzo F, Smith R, Arteel M, et al. Tamoxifen increases nuclear respiratory factor 1 transcription by activating estrogen receptor beta and AP-1 recruitment to adjacent promoter binding sites. FASEB J. 2011;25:1402-16 pubmed publisher..Overall, NRF-1 expression and activity is regulated by 4-OHT via endogenous ER? in MCF-7 cells. ..
- Tsuchiya Y, Morita T, Kim M, Iemura S, Natsume T, Yamamoto M, et al. Dual regulation of the transcriptional activity of Nrf1 by ?-TrCP- and Hrd1-dependent degradation mechanisms. Mol Cell Biol. 2011;31:4500-12 pubmed publisher..Thus, these results clearly suggest that both ?-TrCP- and Hrd1-dependent degradation mechanisms regulate the transcriptional activity of Nrf1 to maintain cellular homeostasis. ..
- Gugneja S, Scarpulla R. Serine phosphorylation within a concise amino-terminal domain in nuclear respiratory factor 1 enhances DNA binding. J Biol Chem. 1997;272:18732-9 pubmedb>Nuclear respiratory factor 1 (NRF-1) is a transcriptional activator that acts on a diverse set of nuclear genes required for mitochondrial respiratory function in mammalian cells...
- Dhar S, Wong Riley M. Coupling of energy metabolism and synaptic transmission at the transcriptional level: role of nuclear respiratory factor 1 in regulating both cytochrome c oxidase and NMDA glutamate receptor subunit genes. J Neurosci. 2009;29:483-92 pubmed publisher..whereby NR1 and possibly other NR subunits and COX are coregulated by the same transcription factor, nuclear respiratory factor 1 (NRF-1), which regulates all COX subunit genes...
- Novotny V, Prieschl E, Csonga R, Fabjani G, Baumruker T. Nrf1 in a complex with fosB, c-jun, junD and ATF2 forms the AP1 component at the TNF alpha promoter in stimulated mast cells. Nucleic Acids Res. 1998;26:5480-5 pubmed..Expression of this altered binding/interaction domain interferes with TNFalpha induction, indicating an interaction of this splice variant with the active AP1/NF-AT complex at this promoter. ..
- Venugopal R, Jaiswal A. Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes. Oncogene. 1998;17:3145-56 pubmed..Nrf2 containing one mutated leucine in its leucine zipper region was more efficient in upregulation of ARE-mediated gene expression, as compared to Nrf1 with two mutated leucines. ..
- Wang W, Kwok A, Chan J. The p65 isoform of Nrf1 is a dominant negative inhibitor of ARE-mediated transcription. J Biol Chem. 2007;282:24670-8 pubmed
- Piantadosi C, Suliman H. Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1. J Biol Chem. 2006;281:324-33 pubmed..This study discloses novel redox regulation of NRF-1 phosphorylation and nuclear translocation by phosphatidylinositol 3,4,5-triphosphate kinase/Akt signaling in controlling Tfam induction by an anti-oxidant pro-survival network. ..
- Chan J, Kwong M, Lu R, Chang J, Wang B, Yen T, et al. Targeted disruption of the ubiquitous CNC-bZIP transcription factor, Nrf-1, results in anemia and embryonic lethality in mice. EMBO J. 1998;17:1779-87 pubmed..To determine the function of Nrf-1, targeted disruption of the Nrf-1 gene was carried out. Homozygous Nrf-1 mutant mice are anemic due to a non-cell autonomous defect in definitive erythropoiesis and die in utero. ..
- Asangani I, Rasheed S, Leupold J, Post S, Allgayer H. NRF-1, and AP-1 regulate the promoter of the human calpain small subunit 1 (CAPNS1) gene. Gene. 2008;410:197-206 pubmed publisher..These results reveal that especially NRF-1, along with AP-1 and, to a minor extent, an Sp1 site, is essential for human CAPNS1 promoter activity and gene expression. ..
- Gonen N, Assaraf Y. The obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1. J Biol Chem. 2010;285:33602-13 pubmed publisher..Bioinformatics identified three putative nuclear respiratory factor 1 (NRF-1) binding sites in the minimal promoter...
- Virbasius J, Scarpulla R. 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. 1994;91:1309-13 pubmed..The activation of the mtTFA promoter by both NRF-1 and NRF-2 therefore provides a link between the expression of nuclear and mitochondrial genes and suggests a mechanism for their coordinate regulation during organelle biogenesis. ..
- Andersson U, Scarpulla R. Pgc-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Mol Cell Biol. 2001;21:3738-49 pubmed..previously been shown to activate mitochondrial biogenesis in part through a direct interaction with nuclear respiratory factor 1 (NRF-1)...
- Chepelev N, Bennitz J, Huang T, McBride S, Willmore W. The Nrf1 CNC-bZIP protein is regulated by the proteasome and activated by hypoxia. PLoS ONE. 2011;6:e29167 pubmed publisher..Collectively, our data suggests that Nrf1 is controlled by several post-translational mechanisms, including ubiquitination, proteolytic processing and proteasomal-mediated degradation as well as by its phosphorylation status. ..
- Han W, Ming M, Zhao R, Pi J, Wu C, He Y. Nrf1 CNC-bZIP protein promotes cell survival and nucleotide excision repair through maintaining glutathione homeostasis. J Biol Chem. 2012;287:18788-95 pubmed publisher..These results indicate a novel role of Nrf1 in UVB-induced DNA damage repair and suggest Nrf1 as a tumor suppressor in the skin. ..
- Zhang L, Ding Q, Wang Z. Nuclear respiratory factor 1 mediates the transcription initiation of insulin-degrading enzyme in a TATA box-binding protein-independent manner. PLoS ONE. 2012;7:e42035 pubmed publisher..The IDE core promoter locates within a 32-bp region, which contains three CGGCG repeats and a nuclear respiratory factor 1 (NRF-1) binding motif...