ライフサイエンスコーパス: IRP1

1 P2) and/or increased IRE-binding activity of IRP1.

2 mpensate for loss of the IRE binding form of IRP1.

3 efficient formation of a [4Fe-4S] cluster on IRP1.

4 d with FBXL5-dependent polyubiquitination of IRP1.

5 smodial sequence has 47% identity with human IRP1.

6 nt effects on promoter activity for IRP3 and IRP1.

7 espectively, than was observed for wild-type IRP1.

8 thout affecting the phosphorylation state of IRP1.

9 ased (3.3-fold) binding affinity of APP mRNA.IRP1.

10 +) eIF4F bound more than 3-times faster than IRP1.

11 Hif-2alpha mRNAs, which preferentially bind IRP1.

12 nderstood about the process of conversion to IRP1.

13 on coupled with induction of an IRP1 mutant (IRP1(3C>3S)) that cannot insert the Fe-S cluster, or alo

14 ed the binding of iron regulatory protein 1 (IRP1), a cytosolic Fe-S protein, to an iron-responsive e

15 pair of cytosolic iron regulatory protein 1 (IRP1), a key regulator of cellular iron homeostasis in m

16 y damaged Fe-S of iron regulatory protein 1 (IRP1), a master regulator of cellular iron that has rece

17 Modulation of IRP1 abundance by iron did not require assembly of the F

18 Mitochondrial and IRP1 aconitase activities were decreased in cells produc

19 ur results reveal a mechanism for regulating IRP1 action relevant to the control of iron homeostasis

20 lates cellular iron metabolism by modulating IRP1 activity.

21 IREs interact with iron response protein1 (IRP1), an iron-dependent translational repressor.

22 ns, iron regulatory protein 1 (also known as IRP1 and Aco1) and iron regulatory protein 2 (also known

23 embling the cytosolic iron-sulfur cluster of IRP1 and activating IRE binding activity, which stabiliz

24 n 21% oxygen, a concentration that activated IRP1 and allowed it to substitute for IRP2.

25 es to examine the solution properties of apo-IRP1 and apo-IRP2 and the interaction with their RNA lig

26 -S cluster assembly in sir animals activated IRP1 and blocked haem biosynthesis catalysed by aminolae

27 th a decrease in the iron regulatory protein IRP1 and intracellular iron overload in skeletal muscle,

28 IRP1 and IRP2 are cytosolic RNA-binding proteins that bi

29 Our data indicate that IRP1 and IRP2 are differentially regulated by NO. in rat

30 The RNA-binding iron regulatory proteins IRP1 and IRP2 are inactivated by either Fe-S cluster ins

31 Although both IRP1 and IRP2 are overexpressed in breast cancer, the ov

32 Although IRP1 and IRP2 are similar proteins in that they are ubiq

33 The two iron regulatory proteins IRP1 and IRP2 bind to transcripts of ferritin, transferr

34 IRP1 and IRP2 binding activities are regulated by intrac

35 We show 1) equivalent IRP1 and IRP2 binding to multiple TfR-IRE RNAs; 2) incre

36 e stem of the ferritin-IRE allows equivalent IRP1 and IRP2 binding.

37 PMA stimulated phosphorylation of IRP1 and IRP2 by at least 2-3-fold without affecting inc

38 Differential regulation of IRP1 and IRP2 during hypoxia may regulate specific IRP t

39 d changes in activity and expression of both IRP1 and IRP2 during phorbol 12-myristate 13-acetate (PM

40 IRP1 and IRP2 expressed in yeast bind the IRE RNA with h

41 n and enhanced IRP2 binding; and 4) variable IRP1 and IRP2 expression in human cells and during devel

42 RNA to assess the relative contributions of IRP1 and IRP2 in epithelial cells.

43 ally regulates the RNA binding activities of IRP1 and IRP2 in human 293 and in mouse Hepa-1 cells.

44 to explore the consequences of loss of both IRP1 and IRP2 in mammalian cells.

45 The role of NO. in the regulation of IRP1 and IRP2 in rat hepatoma cells was investigated by

46 IRP2, we expressed wild-type and mutant rat IRP1 and IRP2 in the yeast Saccharomyces cerevisiae.

47 Because simultaneous knockout of IRP1 and IRP2 is embryonically lethal, it has not been p

48 IRP1 and IRP2 isolated from PMA-treated cells displayed

49 that FBXL5 plays a critical role in limiting IRP1 and IRP2 overaccumulation when cytosolic Fe-S clust

50 L5 expression and a concomitant reduction in IRP1 and IRP2 protein level and RNA-binding activity.

51 Site-directed mutagenesis of IRP1 and IRP2 reveals that, although the binding affinit

52 Effects of multiple IRE interactions with IRP1 and IRP2 were compared between the native TfR-3'-UT

53 TfR) expression and iron-regulatory protein (IRP1 and IRP2) activity.

54 Iron regulatory proteins (IRP1 and IRP2) are master regulators of cellular iron me

55 Iron regulatory proteins (IRP1 and IRP2) are RNA-binding proteins that affect the

56 Iron-regulatory proteins (IRP1 and IRP2) are RNA-binding proteins that bind to ste

57 Iron-regulatory proteins 1 and 2 (IRP1 and IRP2) are RNA-binding proteins that post-transc

58 on, on the iron-regulatory proteins 1 and 2 (IRP1 and IRP2) in a rat hepatoma cell line.

59 c proteins, iron regulatory protein 1 and 2 (IRP1 and IRP2) to stem loop structures, known as iron-re

60 interaction of the iron regulatory proteins (IRP1 and IRP2) with canonical IREs controls iron-depende

61 lements, IREs) and iron-regulatory proteins (IRP1 and IRP2), controlling either mRNA translation or s

62 Two distinct but highly homologous proteins, IRP1 and IRP2, bind IREs with high affinity when cells a

63 There are two known IRPs, IRP1 and IRP2, both of which can respond to iron fluxes

64 There are two identified IRPs, IRP1 and IRP2, each of which binds consensus IREs presen

65 Two IRPs, IRP1 and IRP2, have been identified previously.

66 nsive element (IRE)-binding activity of both IRP1 and IRP2, IFN-gamma treatment decreased IRP2 activi

67 ession via iron regulatory proteins 1 and 2 (IRP1 and IRP2, respectively).

68 d compare the biochemical characteristics of IRP1 and IRP2, we expressed wild-type and mutant rat IRP

69 y regulated by the iron regulatory proteins, IRP1 and IRP2, which regulate proteins involved in iron

70 the actions of the iron regulatory proteins IRP1 and IRP2.

71 ion of iron regulatory RNA-binding proteins, IRP1 and IRP2.

72 lated by the iron regulatory proteins (IRPs) IRP1 and IRP2.

73 IRP1 and IRP6 were repressed under high-iron conditions

74 o maintain cellular iron homeostasis through IRP1 and other pathways is poorly understood.

75 al significance of the aconitase activity of IRP1 and provide insight into the role of c-aconitase wi

76 sion decreases TfR1 expression by inhibiting IRP1 and represses proliferation in pancreatic cancer ce

77 The structure of apo-IRP1 and the mechanism by which it transforms to either

78 the low resolution solution structure of apo-IRP1 and to characterize its biophysical properties.

79 ugh the action of iron regulatory protein 1 (IRP1) and IRP2 coordinate the use of messenger RNA-encod

80 on is mediated by iron regulatory protein 1 (IRP1) and is important for the maintenance of mitochondr

81 ated aberrant mRNA levels of hepcidin, Fpn1, Irp1, and frascati.

82 regulated promoter/operators designated tox, IRP1, and IRP2 were reported previously.

83 embly and dissociation for two IRE-RNAs with IRP1, and quantitatively different metal ion response ki

84 IRP1 knockout (IRP1(-/-)) animals do not significantly misregulate iron

85 sed expression of neural APP consistent with IRP1-APP IRE-driven translation.

86 The activities of IRP1 are mutually exclusive and are modulated through th

87 r cluster explain the alternate functions of IRP1 as an mRNA regulator or enzyme.

88 Therefore, our findings point to IRP1 as the missing link to explain the function of mito

89 Phosphorylation of IRP1 at S138 favored the RNA-binding form and promoted i

90 Phosphorylation of IRP1 at Ser-138 increased when CIA was inhibited and was

91 IRP1 attenuates protoporphyrin biosynthesis by binding t

92 Iron-regulatory protein 1 (IRP1) belongs to a family of RNA-binding proteins that m

93 nterconversion of iron regulatory protein 1 (IRP1) between its RNA binding and cytosolic aconitase (c

94 (50 microM, 25 degrees C) increased IRE-RNA/IRP1 binding (K d) 12-fold (FRT IRE-RNA) or 6-fold (ACO2

95 en bonding and changed RNA conformation upon IRP1 binding and illustrate how small, conserved, sequen

96 IRE-RNA/IRP1 binding changed activation energies: FRT IRE-RNA 47

97 f U, decreased IRP2 binding by >95%, whereas IRP1 binding changed only 13%.

98 croM) decreased the activation energy of RNA-IRP1 binding for both IRE-RNAs.

99 C-G base pair in the terminal loop, whereas IRP1 binding occurs with the C-G or engineered U-A.

100 Mn(2+) decreased kon and increased koff for IRP1 binding to both FRT and ACO2 IRE-RNA, with a larger

101 ce of metal ions was 5-times slower than the IRP1 binding to FRT IRE-RNA.

102 heat, 5 degrees C to 30 degrees C, increased IRP1 binding to IRE-RNA 4-fold (FRT IRE-RNA) or 3-fold (

103 ygen species production, leading to elevated IRP1 binding to IREs.

104 An AGU pseudo-triloop is key for IRP1 binding to the canonical ferritin IREs.

105 of alas2 harboring a mutant IRE, preventing IRP1 binding, in Mfrn1(gt/gt) cells mimics Irp1 deficien

106 ing mRNA activity; Fe(2+) decreases IRE-mRNA/IRP1 binding, increasing encoded protein synthesis.

107 In one mode of operation, IRP1 binds iron-responsive element (IRE) stem-loops in m

108 tions, the cytosolic iron-regulatory protein IRP1 binds to iron-responsive elements (IREs) in mRNAs e

109 Iron regulatory protein 1 (IRP1) binds iron-responsive elements (IREs) in messenger

110 However, as shown earlier with IRP1, both desferrioxamine mesylate and succinyl acetone

111 to paraquat converts cytosolic aconitase to IRP1 but has no affect on mitochondrial aconitase, indic

112 NO. increased IRE binding activity of IRP1, but had no effect on IRE binding activity of IRP2.

113 We show here that the disruption of mouse IRP1, but not IRP2, leads to profound HIF2alpha-dependen

114 nd RNA binding experiments demonstrated that IRP1, but not IRP2, selectively bound the APP IRE in hum

115 Regulation of IRP1 by changing oxygen tension may provide a novel mech

116 on status and can compensate for the loss of IRP1 by increasing its binding activity.

117 Phosphorylation of apo-IRP1 by PKC was specifically inhibited by IRE-containing

118 ntinuing our studies on phosphoregulation of IRP1 by protein kinase C (PKC), we noted that the purifi

119 Knocking down the expression of IRP1 by shRNA abolished the effect of the compounds.

120 an also involve iron-mediated degradation of IRP1 by the E3 ligase FBXL5 that also targets IRP2.

121 ity of the endogenous iron-response protein, IRP1, by 1.9-fold.

122 of PKC-dependent phosphorylation of S711 on IRP1/c-acon function was examined.

123 wherein Ser(138) phosphorylation sensitizes IRP1/c-acon to decreased iron availability by allowing t

124 etween the IRE binding and [4Fe-4S] forms of IRP1 can be modulated independently of cellular iron sta

125 uggest that stability of the Fe-S cluster of IRP1 can be regulated by phosphorylation and reveal a me

126 Furthermore, our results show that IRP1 can function as an oxygen-modulated posttranscripti

127 lts support the view that phosphorylation of IRP1 can modulate its response to iron through effects o

128 Functionally, shRNA knockdown of IRP1 caused increased expression of neural APP consisten

129 The open apo-IRP1 conformation seems optimal for subsequent conversio

130 mino acid domain unique to IRP2 and a mutant IRP1 containing an insertion of this domain bound RNA, b

131 Knockdown of IRP1 decreased IRE binding activity but did not affect f

132 g IRP1 binding, in Mfrn1(gt/gt) cells mimics Irp1 deficiency.

133 -binding activity was primarily regulated by IRP1 degradation in these animals.

134 l sequencing of chymotryptic peptides of apo-IRP1 demonstrated an increased accessibility to proteoly

135 Surprisingly, the RNA-binding activity of IRP1 does not increase in animals on a low-iron diet tha

136 that significant structural changes occur in IRP1 during cluster insertion or removal that affect the

137 Reactivation of IRP1 during reoxygenation was also partially blocked by

138 was previously shown to destabilize IRE-RNA/IRP1 equilibria and enhanced IRE-RNA/eIF4F equilibria.

139 Mfrn1(+/gt);Irp1(-/-) erythroid cells exhibit a significant increase

140 IRP1 exhibits two mutually exclusive functions as an RNA

141 equilibrium experiments have shown that apo-IRP1 exists as an equilibrium mixture of monomers and di

142 Although IRP1 expression rescued aco1 yeast from glutamate auxotr

143 on of the IRE sequence, or downregulation of IRP1 expression, blocks the effect of PGJ(2) on HIF2a tr

144 functional abnormalities along with restored Irp1 expression, improved mitochondrial function and red

145 rent with reduced iron regulatory protein 1 (Irp1) expression as well as increased oxidative stress,

146 ) or IRP1(S138E), which mimic phosphorylated IRP1, failed to give a 3Fe signal.

147 angstrom resolution crystal structure of the IRP1:ferritin H IRE complex shows an open protein confor

148 nitric oxide (NO.) increases the affinity of IRP1 for IREs.

149 nstrated that JTR-009 operated by preventing IRP1 from binding to the IRE in APP mRNA, while maintain

150 Iron regulates IRP1 function by promoting assembly of an iron-sulfur cl

151 us to determine the putative location of the irp1 gene and the positions of irp2, ybtT, and ybtE with

152 The Corynebacterium diphtheriae irp1 gene is negatively regulated by DtxR and iron.

153 Expression of the irp1 gene showed that it encodes a lipoprotein (IRP1) wi

154 y simultaneous deletion of the IRP2, but not IRP1, gene.

155 in which the endogenous expression level of IRP1 greatly exceeds that of IRP2, whereas IRP2-/- mice

156 These results show that apo-IRP1 has a radius of gyration (Rg) of 33.6+/-0.3A, and a

157 presses HIF-2a translation by disrupting the IRP1-HIF-2a IRE interaction.

158 anisms are employed to control the action of IRP1 in dictating changes in the uptake and metabolic fa

159 Much effort has focused on the role of IRP1 in posttranscriptional gene regulation and in facto

160 in rat hepatoma cells, suggesting a role for IRP1 in the regulation of iron homeostasis in vivo durin

161 in IRP1-transformed yeast by >90%, although IRP1 in these cells could be readily converted to c-acon

162 accepted role of iron-regulatory protein 1 (IRP1) in orchestrating the fate of iron-regulated mRNAs

163 thesis inhibitor cycloheximide did not block IRP1 inactivation during hypoxia, it completely blocked

164 IRP1 inactivation was reversible since re-exposure of hy

165 In high-iron conditions, IRP1 incorporates an iron-sulfur cluster (ISC), which in

166 Altogether, this study uncovers a role for IRP1, independent of traditional mechanisms of iron regu

167 n a 4Fe-4S cluster similar to the cluster in IRP1, indicating that they sense iron by different mecha

168 ivo evidence that iron regulatory protein-1 (IRP1) inhibits protoporphyrin accumulation.

169 This selective IRP1 interaction pattern was evident in human brain and

170 ng to the IRE in APP mRNA, while maintaining IRP1 interaction with the H-ferritin IRE RNA stem loop.

171 ransfer to IRP1, recycling the cytosolic apo-IRP1 into holo-aconitase.

172 IRP1/IRE binding occurs through two separate interfaces,

173 IRP1/IRE-RNA complex has a much shorter life-time than t

174 l for providing specificity and stability to IRP1:IRE complex formation.

175 quely to the overall binding affinity of the IRP1:IRE interaction, while one site was found to be uni

176 n of kinetic and thermodynamic properties of IRP1 (iron regulatory protein1) binding to FRT (ferritin

177 IRP1 [iron regulatory protein (IRP) 1] is a bifunctional

178 hesis 4-fold in rabbit reticulocyte lysates (IRP1 + IRP2), confirming differences in IRP2 binding obs

179 In contrast to IRP1, IRP2 was highly phosphorylated in untreated cells.

180 B2 and D), in virulence gene profiles (fyuA, irp1, irp2, chuA, fepC, ibeA, kpsMII, iss), in having a

181 able cell lines were created in which either IRP1, IRP2, or both were knocked down.

182 Mutations in the irp1, irp2, or ybtE gene yielded strains defective in si

183 on between Fe-S cluster assembly, FBXL5, and IRP1/IRP2 activity are poorly defined.

184 Variations in IRE structure and cellular IRP1/IRP2 ratios can provide a range of finely tuned, mR

185 suggest that cluster assembly/disassembly in IRP1 is a dynamic process in aerobically growing yeast.

186 IRP1 is also phosphoregulated by protein kinase C, but t

187 IRP1 is also the cytosolic isoform of aconitase (c-aconi

188 IRP1 is also the cytosolic isoform of aconitase.

189 misregulate iron metabolism, partly because IRP1 is an iron-sulfur protein that functions mainly as

190 There is ample evidence that IRP1 is converted by iron to cytoplasmic aconitase in vi

191 ertain conditions, a significant fraction of IRP1 is degraded in cells exposed to iron or heme.

192 nd rigid-body modeling results show that apo-IRP1 is in an open conformation in solution, and the ens

193 ious X-ray crystallography results show that IRP1 is in an open L-shape conformation when bound to IR

194 In animal tissues, most of the bifunctional IRP1 is in the form of cytosolic aconitase rather than a

195 We conclude that IRP1 is not essential for regulation of ferritin or TfR

196 However, only monomeric IRP1 is observed in complex with IRE.

197 essed in high-iron medium and suggested that irp1 is part of an iron-regulated operon.

198 Our previous work demonstrating that IRP1 is phosphorylated by protein kinase C supported the

199 IRP1 is strongly activated by silencing and genetic muta

200 Our data demonstrate that IRP1 is the principal regulator of HIF2alpha mRNA transl

201 Iron regulatory protein 1 (IRP1) is a bi-functional protein that can act either as

202 Iron-regulatory protein 1 (IRP1) is a dual-function protein with mutually exclusive

203 Iron regulatory protein 1 (IRP1) is regulated through the assembly/disassembly of a

204 cancer, the overexpression of IRP2, but not IRP1, is associated with decreased ferritin H and increa

205 Second, synthesis of IRP2, but not of IRP1, is detectable in Ba/F3-gp55 cells.

206 IRP1 knockout (IRP1(-/-)) animals do not significantly m

207 Striatal ferritin in IRP1 knockout mice was similar to that in wild-type cont

208 jected wild-type striata, was not altered by IRP1 knockout, but was reduced by approximately 60% by I

209 antly increased in IRP2 knockouts but not in IRP1 knockouts.

210 ertension in VhlR200W, Irp1-KO, and VhlR200W;Irp1-KO mice to near normal wild-type levels and normali

211 itigated pulmonary hypertension in VhlR200W, Irp1-KO, and VhlR200W;Irp1-KO mice to near normal wild-t

212 onitase, known as iron regulatory protein 1 (IRP1), led to the characterization of the function of it

213 Thus, 4- to 6-week-old IRP1(-/-) mice exhibit splenomegaly and extramedullary h

214 Flow cytometry of germ cells from WT and Irp1(-/-) mice showed reduction in spermatocytes and rou

215 ocytes and round and elongated spermatids in Irp1(-/-) mice, which was confirmed by histological and

216 egulation of HIF2alpha stability in juvenile IRP1(-/-) mice.

217 olism and develop neurodegeneration, whereas IRP1-/- mice are spared.

218 IRP1-/- mice misregulate iron metabolism only in the kid

219 Iron regulatory protein 1 (IRP1) modulates iron metabolism by binding to mRNAs enco

220 The extended, L-shaped IRP1 molecule embraces the IRE stem-loop through interac

221 evel similar to other murine cell lines, but IRP1 mRNA is not detectable.

222 BXL5 expression coupled with induction of an IRP1 mutant (IRP1(3C>3S)) that cannot insert the Fe-S cl

223 1 yeast expressing wild-type IRP1 or a S138A-IRP1 mutant (IRP1(S138A)), providing the first direct ev

224 The S138E IRP1 mutant and, to a lesser extent, the S138D IRP1 muta

225 P1 mutant and, to a lesser extent, the S138D IRP1 mutant were impaired in aconitase function in yeast

226 ational repression activity of the resulting IRP1 mutants showed that four of the five contact points

227 howed that this cytosolic protein is neither IRP1 nor IRP2.

228 The message (sense) strand of the IRP1 operator (5'-TTAGGTTAGCCAAACCTTT-3') includes the -

229 A T(+7)C variant of the IRP1 operator was also constructed, and it was shown to

230 not of HC3, whereas a clone of the wild-type irp1 operon failed to complement any of these strains.

231 cally grown, aco1 yeast expressing wild-type IRP1 or a S138A-IRP1 mutant (IRP1(S138A)), providing the

232 In short, when iron is depleted, IRP1 or IRP2 bind IREs; this decreases the synthesis of

233 s approach after striatal ICH, the effect of IRP1 or IRP2 gene knockout on ferritin expression and in

234 ns can affect the aconitase activity of holo-IRP1, positively or negatively.

235 iments indicated that transcription from the irp1 promoter is repressed in high-iron medium and sugge

236 Here, we show that IRP1 protein abundance can be iron-regulated.

237 IRP1 protein binds IRE-RNA, inhibiting mRNA activity; Fe

238 IRP1 protein levels were unaffected during hypoxia as we

239 a mammalian cell line that fails to express IRP1 protein or mRNA.

240 vation during hypoxia, it completely blocked IRP1 reactivation during subsequent reoxygenation.

241 romptly to initiate Fe/S cluster transfer to IRP1, recycling the cytosolic apo-IRP1 into holo-aconita

242 w that Drosophila iron regulatory protein-1 (IRP1) registers cytosolic iron and oxidative stress thro

243 of SIRT3 in cellular iron metabolism through IRP1 regulation and suggest that SIRT3 functions as a tu

244 A motif in the terminal loop did not bind to IRP1 relative to wild type probes and could no longer ba

245 hout the 5' iron response element that binds IRP1 rescued sir embryos, whereas overexpression of ALAS

246 Further, antisense knockdown of IRP1 restored sir embryo haemoglobin synthesis.

247 The nucleotide sequence of irp1 revealed that it has homology with genes involved i

248 d molecular docking analysis of APP IRE mRNA.IRP1 reveals that 11 residues are involved in hydrogen b

249 These data demonstrate that IRP1 RNA binding activity is post-translationally regula

250 st to IRP1, where hypoxic exposure decreases IRP1 RNA binding activity, hypoxia increases IRP2 RNA bi

251 Inactivation of IRP1 RNA binding by iron primarily involves insertion of

252 In cells exposed to hypoxia, IRP1 RNA binding was decreased approximately 2.8-fold af

253 phases during hypoxia: an early phase where IRP1 RNA-binding activity decreases and iron uptake and

254 IRP1 RNA-binding activity was primarily regulated by IRP

255 is in Mfrn1(gt/gt) cells results in elevated IRP1 RNA-binding that attenuates ALAS2 mRNA translation

256 ssing wild-type IRP1 or a S138A-IRP1 mutant (IRP1(S138A)), providing the first direct evidence of a 3

257 Yeast expressing IRP1(S138D) or IRP1(S138E) were the most sensitive to in

258 Untreated yeast expressing IRP1(S138D) or IRP1(S138E), which mimic phosphorylated I

259 oduced a weak 3Fe signal in yeast expressing IRP1(S138D).

260 c conditions cluster insertion into purified IRP1(S138E) and cluster loss on treatment with NO regula

261 Yeast expressing IRP1(S138D) or IRP1(S138E) were the most sensitive to inhibition of aco

262 binding and aconitase forms was observed for IRP1(S138E) when expressed in HEK cells.

263 Untreated yeast expressing IRP1(S138D) or IRP1(S138E), which mimic phosphorylated IRP1, failed to

264 In its other mode, IRP1 serves as cytoplasmic aconitase to correlate iron a

265 olism by influencing the cytosolic aconitase-IRP1 switch, redistributes iron from the cytosol to mito

266 As a consequence, IRP1 target genes, such as the transferrin receptor (TfR

267 r spermatid maturation, was less frequent in Irp1(-/-) testicular cross-sections.

268 Studies have shown that the degradation of IRP1 that is induced by iron can be inhibited by either

269 Like IRP1, the RNA-binding activity of IRP2 was sensitive to

270 IRP1, the well-characterized IRP in cells, is a dual-fun

271 e iron-regulated promoters (IRPs) designated IRP1 through IRP5 as well as from the promoters for the

272 ry protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element.

273 ions in genes required for the conversion of IRP1 to c-aconitase led to the identification of a previ

274 e compare the effects of genetic ablation of IRP1 to IRP2 in mice.

275 Here we demonstrate an incomplete shift of IRP1 to its ISC form in Friedreich ataxia (FRDA) fibrobl

276 cellular iron chelation increased binding of IRP1 to the APP IRE, decreasing intracellular APP expres

277 ng the binding of iron regulatory protein-1 (IRP1) to a noncanonical iron responsive element (IRE) em

278 ng the binding of Iron-Regulatory Protein 1 (IRP1) to a recently reported iron-responsive element (IR

279 , vertebrates use iron regulatory protein 1 (IRP1) to sense intracellular iron and regulate mRNA stab

280 he binding of the iron regulatory protein 1 (IRP1) to the iron response element (IRE), and of HIV tra

281 IRP1-transformed cfd1-1 yeast lacked EPR-detectable Fe-S

282 -1) reduced c-aconitase specific activity in IRP1-transformed yeast by >90%, although IRP1 in these c

283 Hypoxic inactivation of IRP1 was abolished when cells were pretreated with the i

284 The increase in IRE binding activity of IRP1 was coincident with the translational repression of

285 in of animals maintained on the Tempol diet, IRP1 was converted from a cytosolic aconitase to an IRE

286 kon, for FRT IRE-RNA binding to IRP1 was eight times faster than ACO2 IRE-RNA.

287 Finally, reactivated IRP1 was found to be resistant to inactivation by exogen

288 In yeast, the c-aconitase activity of IRP1 was responsive to iron availability in the growth m

289 ding) activity of iron regulatory protein 1 (IRP1) was activated, and increased IRP2 levels, indicati

290 analogous to those used previously to study IRP1, we find that IRP2 is degraded in rabbit fibroblast

291 from IRP6 and previously described promoter IRP1 were found to encode proteins homologous to compone

292 mined the importance of FBXL5 for regulating IRP1 when CIA is impaired.

293 In contrast to IRP1, where hypoxic exposure decreases IRP1 RNA binding

294 However, unlike IRP1, where reconstitution of the 4Fe-4S cluster resulte

295 of APP mRNA with iron-regulatory protein-1 (IRP1) whereas IRP2 controls the mRNAs encoding the L- an

296 icate that the small RNA-binding fraction of IRP1, which is insensitive to cellular iron status, cont

297 y of a [4Fe-4S] cluster, which interconverts IRP1 with cytosolic aconitase.

298 1 gene showed that it encodes a lipoprotein (IRP1) with a predicted size of 38 kDa.

299 nterconversion of iron regulatory protein 1 (IRP1) with cytosolic aconitase (c-aconitase) occurs via

300 ctivity over a similar range as observed for IRP1(WT).