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 d with FBXL5-dependent polyubiquitination of IRP1.

4 efficient formation of a [4Fe-4S] cluster on 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 +) eIF4F bound more than 3-times faster than IRP1.

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

11 nderstood about the process of conversion to IRP1.

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

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

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

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

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

17 Mitochondrial and IRP1 aconitase activities were decreased in cells produc

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

19 lates cellular iron metabolism by modulating IRP1 activity.

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

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

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

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

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

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

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

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

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

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

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

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

32 IRP1 and IRP2 binding activities are regulated by intrac

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

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

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

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

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

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

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

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

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

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

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

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

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

46 IRP1 and IRP2 isolated from PMA-treated cells displayed

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

71 IRP1 and IRP6 were repressed under high-iron conditions

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

88 IRP1 attenuates protoporphyrin biosynthesis by binding t

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

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

91 (50 microM, 25 degrees C) increased IRE-RNA/IRP1 binding (K d) 12-fold (FRT IRE-RNA) or 6-fold (ACO2

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

134 Reactivation of IRP1 during reoxygenation was also partially blocked by

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

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

137 IRP1 exhibits two mutually exclusive functions as an RNA

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

139 Although IRP1 expression rescued aco1 yeast from glutamate auxotr

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

159 IRP1 inactivation was reversible since re-exposure of hy

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

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

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

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

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

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

166 IRP1/IRE binding occurs through two separate interfaces,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

182 IRP1 is also the cytosolic isoform of aconitase.

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

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

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

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

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

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

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

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

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

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

193 IRP1 is strongly activated by silencing and genetic muta

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

213 1 yeast expressing wild-type IRP1 or a S138A-IRP1 mutant (IRP1(S138A)), providing the first direct ev

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

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

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

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

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

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

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

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

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

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

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

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

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

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

228 IRP1 protein levels were unaffected during hypoxia as we

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

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

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

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

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

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

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

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

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

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

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

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

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

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

243 IRP1 RNA-binding activity was primarily regulated by IRP

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

285 1 gene showed that it encodes a lipoprotein (IRP1) with a predicted size of 38 kDa.

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

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