ライフサイエンスコーパス: NRF-1

1 NRF-1 and NRF-2 act additively while NRF-2 synergizes wi

2 NRF-1 and Sp1 are known to bind and stimulate the active

3 NRF-1 binding sites on Grin1 and Grin2b genes are also h

4 NRF-1 expression and growth were restored by exogenous o

5 NRF-1 functionally regulates mediators of energy consump

6 NRF-1 gene silencing blocked aerobic succinate oxidation

7 NRF-1 gene silencing produced 1:1 knockdown of Tfam expr

8 NRF-1 regulates mediators of neuronal activity and energ

9 NRF-1 transcriptionally regulates Na(+)/K(+)-ATPase subu

10 NRF-1 was required for stable binding of Sp1.

11 NRF-1, cAMP response element, and Sp-1 site mutations wi

12 NRF-1-Tfam binding was augmented under pro-oxidant condi

13 interact with nuclear respiratory factor 1 (NRF-1) and activate NRF-1 target genes required for resp

14 owed that both nuclear respiratory factor 1 (NRF-1) and cAMP-response element-binding protein (CREB)

15 ncluding human nuclear respiratory factor 1 (NRF-1) and the sea urchin P3A2 protein.

16 ns a conserved nuclear respiratory factor 1 (NRF-1) binding site.

17 ave implicated nuclear respiratory factor 1 (NRF-1) in the transcriptional expression of nuclear gene

18 Nuclear respiratory factor 1 (NRF-1) is a nuclear transcription factor that has been i

19 Nuclear respiratory factor 1 (NRF-1) is a transcriptional activator of nuclear genes t

20 Nuclear respiratory factor 1 (NRF-1) is a transcriptional activator that acts on a div

21 Nuclear respiratory factor 1 (NRF-1) is one of the key transcriptional activators for

22 ypothesis that nuclear respiratory factor 1 (NRF-1) serves such a role in subunit coordination.

23 ription factor nuclear respiratory factor 1 (NRF-1) to the cytochrome c promoter and NRF-2 to the cyt

24 tive allele of nuclear respiratory factor 1 (NRF-1), and glucose deprivation.

25 iption factor, nuclear respiratory factor 1 (NRF-1), found recently by our laboratory to regulate all

26 ding sites for nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2/GA binding protein

27 Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial gene

28 iption factor, nuclear respiratory factor 1 (NRF-1), which regulates all COX subunit genes.

29 teraction with nuclear respiratory factor 1 (NRF-1).

30 , c-jun, JunB, nuclear respiratory factor 1 (NRF-1)], mitochondrial proliferation [cytochrome c (Cyt

31 species, i.e. nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor-A.

32 tional Sp1 and nuclear respiratory factor-1 (NRF-1) elements within a GC-rich proximal GluR2 promoter

33 Nuclear respiratory factor-1 (NRF-1) is integral to the transcriptional regulation of

34 a TATA box, a nuclear respiratory factor-1 (NRF-1) site, and two GC boxes.

35 s bound by the nuclear respiratory factor-1 (NRF-1) transcription factor.

36 (E(2)) induces nuclear respiratory factor-1 (NRF-1) transcription through ERalpha in MCF-7 breast can

37 these genes - nuclear respiratory factor-1 (NRF-1) was significantly up-regulated during the 4-OH-E2

38 on of multiple nuclear respiratory factor-1 (NRF-1)-dependent genes encoding key enzymes in oxidative

39 fic binding to nuclear respiratory factor-1 (NRF-1).

40 1 (PGC-1), and nuclear respiratory factor-1 (NRF-1).

41 ription factor nuclear respiratory factor-1 (NRF-1).

42 nB, as well as nuclear respiratory factor-1 (NRF-1).

43 sted the hypothesis that increases in PGC-1, NRF-1, and NRF-2 are involved in the initial adaptive re

44 se findings suggest that increases in PGC-1, NRF-1, and NRF-2 represent key regulatory components of

45 tubes induces increased expression of PGC-1, NRF-1, NRF-2, and mtTFA, factors that have been implicat

46 to HC, coupled to a reduction in PGC-1alpha, NRF-1, Nrf2, TFam, mfn2 and SOD1/2 gene expression.

47 activity, mRNA expression of the PGC-1alpha, NRF-1, Tfam and CytC genes, mitochondrial DNA content, m

48 mitochondrial biogenesis pathway (PGC-1alpha/NRF-1).

49 vels for nuclear respiratory factor 1 and 2 (NRF-1 and -2), the proteins that are known to interact w

50 Nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2) are ubiquitous transcription factors th

51 n mitochondrial biogenesis (PGC-1alpha, 55%; NRF-1, 15%; TFAM, 85%).

52 es arranged in a tandem repeat, as well as a NRF-1 site and an Sp1 site.

53 Mutagenesis studies revealed that a NRF-1 site is especially important for the basal and ind

54 at which site-directed mutagenesis abolished NRF-1 phosphorylation by Akt.

55 ar respiratory factor 1 (NRF-1) and activate NRF-1 target genes required for respiratory chain expres

56 shown to interact with NRF-1 and co-activate NRF-1.

57 PRC activated NRF-1-dependent promoters in a manner similar to that ob

58 eased nuclear respiratory factor activation (NRF-1 and NRF-2) and Tfam, TFB1M, and TFB2M mRNA express

59 Although NRF-1 can dimerize in the absence of DNA, phosphorylatio

60 Although NRF-1 expression is decreased only in diabetic subjects,

61 n was accounted for by point mutations in an NRF-1 site and either of two flanking sites for Sp1.

62 , which is consistent with the absence of an NRF-1 consensus sequence in the proximal rat promoter.

63 litated expression via a "cargo" of AP-1 and NRF-1 transcription factors and TALE-based transcription

64 ed staining intensity with rhodamine 123 and NRF-1(-/-) blastocysts had markedly reduced levels of mi

65 lear-encoded metabolic genes, PGC-1alpha and NRF-1, was also observed in Stat3-null keratinocytes; ho

66 chondrial biogenesis markers (PGC1-alpha and NRF-1) in the cerebella of IP6K2-deleted mice (IP6K2-kno

67 Both CREB and NRF-1 bind the same sites on PRC, and the interaction wi

68 Moreover, CREB and NRF-1 were phosphorylated sequentially in response to se

69 g dominant-negative NRF-1 overexpression and NRF-1 small interfering RNA knockdown.

70 Finally, Akt phosphorylation and NRF-1 translocation predictably lacked oxidant regulatio

71 luR2 promoter activity required both Sp1 and NRF-1 cis elements and an interelement nucleotide bridge

72 osphorylated RNA polymerase II, YY1, Sp1 and NRF-1, further suggesting a key role for NRF-1 in regula

73 While most isolated wild-type and NRF-1(+/-) blastocysts can develop further in vitro, the

74 rs (TFs) SP1, NF-Y, ETS, CREB, TBP, USF, and NRF-1.

75 om HepG2 cell nuclear extract, identified as NRF-1 and Sp1, bound to the promoter at sites within the

76 d competition experiments with the authentic NRF-1 and NRF-2 DNA oligomers from previously characteri

77 f ERbeta revealed that ERbeta inhibits basal NRF-1 expression and is required for 4-OHT-induced NRF-1

78 s through cis-acting elements that bind both NRF-1 and CREB.

79 o the collection of genes controlled by both NRF-1 and NRF-2 and disfavor its membership in the immed

80 The activation domains of both NRF-1 and NRF-2 were extensively characterized by both d

81 DNA-bound NRF-1 can form a complex with PARP-1, suggesting that NR

82 a role during transcriptional activation by NRF-1.

83 regulation of a signal transduction gene by NRF-1.

84 5 is the first gene shown to be regulated by NRF-1 that possesses an expression profile during embryo

85 Atp1b1 is positively regulated by NRF-1, and silencing of NRF-1 with small interference RN

86 ther hand, Atp1a1 is negatively regulated by NRF-1.

87 onal domains required for transactivation by NRF-1 have been defined.

88 aspect of transcriptional regulation used by NRF-1.

89 Moreover, a CREB/NRF-1 interaction domain on PRC is required for its tran

90 noprecipitation provided evidence for direct NRF-1 binding to the VSNL1 promoter.

91 of motifs, including GABPA, MYC, E2F1, E2F4, NRF-1, CCAAT, YY1, and ACTACAnnTCC are overrepresented i

92 with high developmental expression of either NRF-1 (brown fat and developing brain) or myogenin (stri

93 with transcription factors such as ERRalpha, NRF-1, and HNF4alpha, however acetylation and transcript

94 iants of six known CpG-containing TFBS: ETS, NRF-1, BoxA, SP1, CRE, and E-Box.

95 data from 29 tissues indicate that the ETS, NRF-1, and Clus1 sequences that cluster are predominantl

96 rate that methylation of the CpG in the ETS, NRF-1, and SP1 motifs prevent DNA binding in nuclear ext

97 nscriptional activity suggests that the EWG, NRF-1, and P3A2 family of proteins shares common mechani

98 e data suggest that the transcription factor NRF-1 plays a key role in cellular adaptation to energy

99 osphorylation of nuclear respiratory factor (NRF-1) and binding to the Tfam promoter.

100 RC1 and PCNA, and the transcription factor - NRF-1.

101 al sites for the nuclear respiratory factors NRF-1 and NRF-2 were identified.

102 ns sites for the nuclear respiratory factors NRF-1 and NRF-2, which have been shown to contribute to

103 regulated by the nuclear respiratory factors NRF-1 and NRF-2.

104 mediated by binding of transcription factors NRF-1 and CCAAT/enhancer-binding protein delta (C/EBP) t

105 is governed by nuclear respiratory factors (NRF-1 and NRF-2), key transcription factors implicated i

106 Embryos homozygous for NRF-1 disruption die between embryonic days 3.5 and 6.5.

107 spiration, but only if translatable mRNA for NRF-1 is available.

108 e consistent with a specific requirement for NRF-1 in the maintenance of mtDNA and respiratory chain

109 These results support a regulatory role for NRF-1 and possibly AP-1 in the initiation of mitochondri

110 and NRF-1, further suggesting a key role for NRF-1 in regulation of the SNRPN locus.

111 reover, genetic evidence supports a role for NRF-1 in the maintenance of mtDNA during embryonic devel

112 These findings disclose a novel role for NRF-1 in the transcriptional control of Complex II and p

113 ptosis, indicating an antiapoptotic role for NRF-1.

114 Notably, recognition sites for NRF-1, NRF-2 and Sp1 are common to most nuclear genes en

115 etic mobility shift assay using a functional NRF-1 binding site from the delta-aminolevulinate (ALA)

116 , PGC-1alpha and the PGC-1alpha target gene, NRF-1 by binding to insulin response sequences in the PG

117 The HBZ/NRF-1/TDP1 axis provides new therapeutic targets against

118 tially by c-jun (0.5-3 hr), JunB (0.5-6 hr), NRF-1 (1-12 hr), Cyt c (12-72 hr), and muscle-specific C

119 s to sequence heterogeneity within the human NRF-1 5'-untranslated region (UTR).

120 47kb, bringing the total length of the human NRF-1 gene to approx. 104kb.

121 These exons were mapped to human NRF-1 genomic clones and their sequences, including dono

122 ilencing, and chromatin immunoprecipitation, NRF-1 was found to bind to the gene promoters of two of

123 A 10 out of 12 imperfect NRF-1 site was located within the first exon.

124 synthase was increased approximately 50% in NRF-1 transgenic muscle.

125 in PGC-1 and mtTFA protein expression and in NRF-1 and NRF-2 binding to DNA.

126 ent 5'-UTR exons (UTRs 1-6) were detected in NRF-1 transcripts.

127 se results show that an isolated increase in NRF-1 is not sufficient to bring about a coordinated inc

128 nsumption was associated with an increase in NRF-1 mRNA.

129 It was also associated with an increase in NRF-1 protein binding activity as determined by electrop

130 The 4-OHT-induced increase in NRF-1 resulted in increased transcription of NRF-1 targe

131 pression of MEF2A and GLUT4 was increased in NRF-1 transgenic muscle.

132 2 (Gabpa), and MEF2, and for IL1Ra, included NRF-1 and MEF2.

133 veral sequence-specific activators including NRF-1, NRF-2, Sp1, YY1, CREB and MEF-2/E-box factors, am

134 with multiple regulatory proteins, including NRF-1, which regulates genes involved in mitochondrial a

135 ut not CYC1, CYC2, or TFAM despite increased NRF-1 coactivator PGC-1alpha protein.

136 4-OHT), with an EC(50) of ~1.7 nM, increases NRF-1 expression by recruiting ERbeta, cJun, cFos, CBP,

137 bility shift and supershift assays indicated NRF-1 binding to all ten promoters.

138 An AP-1 inhibitor blocked 4-OHT-induced NRF-1 expression.

139 expression and is required for 4-OHT-induced NRF-1 transcription.

140 -1 site contributes to maximal 4-OHT-induced NRF-1 transcription.

141 esis in rat liver, we found that LPS induces NRF-1 protein expression and activity accompanied by mRN

142 HBZ suppresses TDP1 expression by inhibiting NRF-1 function in ATL cells.

143 Overexpression of full-length NRF-1 and a dominant-negative form of NRF-1 modulated re

144 Here, we demonstrate that, like NRF-1, CREB binds PRC in vitro and exists in a complex w

145 higher hepatic TNF-alpha mRNA levels, lower NRF-1 and PGC-1alpha mRNA levels, and no enhancement of

146 Mutations within human UTR1 modulate NRF-1 expression by interfering with mRNA translational

147 Moreover, NRF-1 is known to activate mitochondrial transcription f

148 Moreover, NRF-1 was immunoprecipitated from cell extracts by antib

149 The exercise induced increases in muscle NRF-1 and NRF-2 that were evident 12 to 18 h after one e

150 Like c-Myc, NRF-1 overexpression sensitizes cells to apoptosis on se

151 stress was also induced by dominant negative NRF-1 and by glucose deprivation, suggesting that divers

152 site and transfection of a dominant-negative NRF-1 both revealed the crucial role of NRF-1 in activat

153 as further confirmed using dominant-negative NRF-1 overexpression and NRF-1 small interfering RNA kno

154 -1 target genes by using a dominant-negative NRF-1 prevented c-Myc-induced apoptosis, without affecti

155 hereas the introduction of dominant-negative NRF-1 repressed such activity.

156 The ensuing accumulation of nuclear NRF-1 protein leads to gene activation for mitochondrial

157 RF-1 and inhibits the DNA-binding ability of NRF-1.

158 Activation of NRF-1 in fibroblasts has been shown to induce increases

159 eraction with NRF-1 and in the activation of NRF-1 target genes.

160 finding is consistent with the appearance of NRF-1 and fos/jun mRNAs prior to that of Cyt c and sugge

161 Physical association of NRF-1 protein with the NRF-1 enhancer element and of c-J

162 Specific binding of NRF-1 to Tfam promoter was demonstrated by electrophoret

163 PPARGC1 and PGC1-beta/PERC), coactivators of NRF-1 and PPAR gamma-dependent transcription, is decreas

164 can also PARylate the DNA-binding domain of NRF-1 and negatively regulate NRF-1.PARP-1 interaction.

165 show that DNA-binding/dimerization domain of NRF-1 and the N-terminal half of PARP-1, which contains

166 Moreover, the embryonic expression of NRF-1 did not result from maternal carryover.

167 length NRF-1 and a dominant-negative form of NRF-1 modulated reporter gene expression driven by the c

168 We investigated here the in vivo function of NRF-1 in mammals by disrupting the gene in mice.

169 coactivates the transcriptional function of NRF-1 on the promoter for mitochondrial transcription fa

170 The function of NRF-1 was further confirmed using dominant-negative NRF-

171 binding sites confirmed the functionality of NRF-1 binding on all ten COX promoters.

172 binding sequence (T/C)GCGCA(C/T)GCGC(A/G) of NRF-1 includes a noncanonical CA(C/T)GCG Myc:MAX binding

173 is the first demonstration that induction of NRF-1 and c-Jun by pacing of cardiac myocytes directly m

174 PGC-1 stimulates a powerful induction of NRF-1 and NRF-2 gene expression; in addition, PGC-1 bind

175 we establish a link between the induction of NRF-1 target genes and sensitization to apoptosis on ser

176 lective interference with c-Myc induction of NRF-1 target genes by using a dominant-negative NRF-1 pr

177 OHT-induced apoptosis and siRNA knockdown of NRF-1 increased apoptosis, indicating an antiapoptotic r

178 nished oxidant production and caused loss of NRF-1 expression and growth delay.

179 Overexpression of NRF-1 also upregulated endogenous TDP-1 expression, whil

180 Overexpression of NRF-1 increased TDP1-promoter activity, whereas the intr

181 Overexpression of NRF-1 inhibited 4-OHT-induced apoptosis and siRNA knockd

182 b1 induced by KCl, whereas overexpression of NRF-1 rescued these transcripts from being suppressed by

183 nd COX induced by KCl, and overexpression of NRF-1 rescued these transcripts that were suppressed by

184 o a lack of Akt-dependent phosphorylation of NRF-1 with 4-OHT treatment.

185 te oxidation-reduction (redox) regulation of NRF-1 in Tfam expression, blockade of upstream phosphati

186 is study discloses novel redox regulation of NRF-1 phosphorylation and nuclear translocation by phosp

187 tive NRF-1 both revealed the crucial role of NRF-1 in activation of P1.

188 To further evaluate the role of NRF-1 in the regulation of mitochondrial biogenesis and

189 t provides new insight regarding the role of NRF-1 was that expression of MEF2A and GLUT4 was increas

190 Silencing of NRF-1 with RNA interference reduced all ten COX subunit

191 itively regulated by NRF-1, and silencing of NRF-1 with small interference RNA blocked the up-regulat

192 However, silencing of NRF-1 with small interference RNA blocked the upregulati

193 The binding sites of NRF-1 on Atp1a1 and Atp1b1 are conserved among mice, rat

194 o demonstrate loss of oxidant stimulation of NRF-1 phosphorylation and Tfam expression.

195 NRF-1 resulted in increased transcription of NRF-1 target CAPNS1 but not CYC1, CYC2, or TFAM despite

196 g positive correlation between PGC-1alpha or NRF-1 and long IDE isoform transcripts was found in non-

197 Overall, NRF-1 expression and activity is regulated by 4-OHT via

198 ria-rich rat hepatoma cells that overexpress NRF-1, basal and oxidant-induced increases were found in

199 ted from rat hepatoma cells that overexpress NRF-1.

200 we generated transgenic mice overexpressing NRF-1 in skeletal muscle.

201 al analysis, and real-time quantitative PCR, NRF-1 was found to functionally bind to the promoters of

202 r mutations, and real-time quantitative PCR, NRF-1 was found to functionally bind to the promoters of

203 Cyclin D1-dependent kinase phosphorylates NRF-1 at S47.

204 Site-directed mutagenesis of putative NRF-1 binding sites confirmed the functionality of NRF-1

205 ated in vitro by phosphorylating recombinant NRF-1 with purified casein kinase II.

206 ding domain of NRF-1 and negatively regulate NRF-1.PARP-1 interaction.

207 matin immunoprecipitation assays also showed NRF-1 binding to all ten promoters in murine neuroblasto

208 SIGNIFICANCE: NRF-1 mediates the tight coupling of neuronal activity,

209 ing sites for the transcription factors Sp1, NRF-1, and NRF-2.

210 We conclude that Sp1, NRF-1, and NRF-2 are important in activating transcripti

211 TA and Inr), several known motifs (YY1, Sp1, NRF-1, NRF-2, CAAT, and CREB) and one potentially new mo

212 1 promotes mitochondrial biogenesis and that NRF-1 and NRF-2 act as transcriptional activators of gen

213 We conclude that NRF-1 plays a significant role in coordinating the trans

214 Here, we establish that NRF-1 is a phosphoprotein in vivo.

215 genes, but there is no direct evidence that NRF-1 transduces a physiological signal into the product

216 We show here that NRF-1 can also directly interact with poly(ADP-ribose) p

217 osphorylation, we tested the hypothesis that NRF-1 regulates Complex II expression and opposes hypoxi

218 The findings indicate that NRF-1 and NRF-2 utilize similar hydrophobic structural m

219 These results indicate that NRF-1 is a positive transcriptional regulator of TDP1-ge

220 Our results further indicated that NRF-1 could be a regulatory factor for gene expression o

221 They also provide the new information that NRF-1 overexpression results in increased expression of

222 We postulated that NRF-1 suppression either specifically decreases the expr

223 We propose that NRF-1, which has been shown by others to be expressed du

224 form a complex with PARP-1, suggesting that NRF-1 can recruit the PARP-1.DNA-PK.Ku80.Ku70.topoisomer

225 d sequentially in response to serum, and the NRF-1 phosphorylation was accompanied by an increase in

226 ence suggesting that interaction between the NRF-1 site and an upstream element contributes to expres

227 We show that both the NRF-1 and NRF-2 binding sites are functional in COX7AL a

228 Mutations in either the NRF-1 or in the two cyclic AMP response elements on the

229 Mutations in the NRF-1 and CRE sites inhibited the induction by electrica

230 lation results in an intrinsic change in the NRF-1 dimer enhancing its ability to bind DNA.

231 antioxidant response elements (AREs) in the NRF-1 promoter.

232 espiratory capacity was not increased in the NRF-1 transgenic mice.

233 insertions of Alu-sq family members into the NRF-1 locus.

234 Examination of the NRF-1 amino acid sequence revealed an Akt phosphorylatio

235 A portion of the NRF-1 gene that encodes the nuclear localization signal

236 igonucleotide antisense to the region of the NRF-1 initiation codon; a scrambled oligonucleotide with

237 idase expression is under the control of the NRF-1 promoter.

238 Methylation of the NRF-1-binding site was found to be able to regulate VSNL

239 l hydrophobic motifs within 40 residues, the NRF-1 domain spans about 40% of the molecule and appears

240 3.5-day-old embryos, demonstrating that the NRF-1 gene is expressed during oogenesis and during earl

241 Site-directed mutagenesis showed that the NRF-1 site is crucial for promoter activity providing th

242 Specific factor binding to the NRF-1 site and GC boxes were demonstrated by gel mobilit

243 lastocysts can develop further in vitro, the NRF-1(-/-) blastocysts lack this ability despite their n

244 PRC interacts in vitro with the NRF-1 DNA binding domain through two distinct recognitio

245 ysical association of NRF-1 protein with the NRF-1 enhancer element and of c-Jun with the cyclic AMP

246 ter did not form a specific complex with the NRF-1 in the liver or hepatoma nuclear extracts, which i

247 entify related coactivators that act through NRF-1, we searched the databases for sequences with simi

248 onal relative of PGC-1 that operates through NRF-1 and possibly other activators in response to proli

249 Thus, NRF-1 and our previously described NRF-2 prove to be the

250 Thus, NRF-1 is an essential transcription factor critical in t

251 Thus, NRF-1 regulates key Na(+)/K(+)-ATPase subunits and plays

252 Thus, NRF-1 was implicated in oxidant-mediated mitochondrial b

253 ere cloned from the screen were identical to NRF-1, a result that was confirmed by further electropho

254 ive stress stimulates biogenesis in part via NRF-1 activation and corresponding to recovery events af

255 that it is a third common factor, along with NRF-1 and NRF-2, to be associated with COX gene regulati

256 have previously been shown to interact with NRF-1 and co-activate NRF-1.

257 to PGC-1, especially in its interaction with NRF-1 and in the activation of NRF-1 target genes.

258 is in part through a direct interaction with NRF-1.

259 d in all ATL cases physically interacts with NRF-1 and inhibits the DNA-binding ability of NRF-1.

260 On the basis of its similarity with NRF-1 and IBR, nrf is likely involved in transcriptional