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1 set1A, P = 0.029 for aatA, and P = 0.04 for irp2).
2 on metabolism via iron regulatory protein 2 (IRP2).
3 bolism, including iron regulatory protein 2 (IRP2).
4 tabolism genes by iron regulatory protein 2 (IRP2).
5 ons of the iron regulatory proteins IRP1 and IRP2.
6 on regulatory RNA-binding proteins, IRP1 and IRP2.
7 low-iron diet that is sufficient to activate IRP2.
8 ivated IRP1 and allowed it to substitute for IRP2.
9 s in the gene IREB2 leading to an absence of IRP2.
10 raded at a rate similar to that of wild-type IRP2.
11 t this cytosolic protein is neither IRP1 nor IRP2.
12 the iron regulatory proteins (IRPs) IRP1 and IRP2.
13 ivity in Ba/F3-gp55 cells is attributable to IRP2.
14 ed to reduce the abundance of phosphorylated IRP2.
15 but had no effect on IRE binding activity of IRP2.
16 RP1 by the E3 ligase FBXL5 that also targets IRP2.
17 composed of a stable but inactive species of IRP2.
18 ron metabolism and is largely independent on IRP2.
19 affinity of the HIF2alpha IRE for IRP1 than IRP2.
20 5 C-terminal loop responsible for recruiting IRP2.
21 lation was suppressed by FDXR deficiency via IRP2.
22 -dependent ubiquitination and degradation of IRP2.
23 cells, in part by iron regulatory protein 2 (IRP2), a protein that is degraded efficiently by the pro
24 that mice lacking iron-regulatory protein 2 (Irp2), a regulator of cellular iron homeostasis, develop
26 transcriptional activation by HIF-1, because IRP2 accumulates in Hepa-1 cells lacking a functional HI
27 on availability, accompanied by constitutive IRP2 accumulation and misexpression of IRP2 target genes
30 cytosolic aconitase in mammalian tissues and IRP2 activity increases to compensate for loss of the IR
34 P2s lacking a 73 amino acid domain unique to IRP2 and a mutant IRP1 containing an insertion of this d
35 n of IRP2 have employed cells overexpressing IRP2 and also rendered iron deficient to further increas
36 nt p53 gain-of-function can be suppressed by IRP2 and FDXR deficiency, both of which may be explored
38 and iron regulatory protein 2 (also known as IRP2 and Ireb2), sense cytosolic iron levels and posttra
40 the solution properties of apo-IRP1 and apo-IRP2 and the interaction with their RNA ligand, the iron
41 reased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-
42 creased levels of iron regulatory protein 2 (IRP2) and/or increased IRE-binding activity of IRP1.
47 NA-binding iron regulatory proteins IRP1 and IRP2 are inactivated by either Fe-S cluster insertion or
53 Iron-regulatory proteins 1 and 2 (IRP1 and IRP2) are RNA-binding proteins that post-transcriptional
54 nrichment clustering analysis, we identified Irp2 as a regulator of mitochondrial function in the lun
55 d iron-responsive element-binding protein 2 (IRP2) as an important COPD susceptibility gene and have
58 In short, when iron is depleted, IRP1 or IRP2 bind IREs; this decreases the synthesis of proteins
59 The two iron regulatory proteins IRP1 and IRP2 bind to transcripts of ferritin, transferrin recept
60 nct but highly homologous proteins, IRP1 and IRP2, bind IREs with high affinity when cells are deplet
65 RE to a C-bulge, by deletion of U, decreased IRP2 binding by >95%, whereas IRP1 binding changed only
66 ntribution of the IRE internal loop/bulge to IRP2 binding by comparing natural and engineered IRE var
72 each TfR-IRE folds into an IRE that has low IRP2 binding, whereas a loop/bulge in the stem of the fe
74 with ferritin-IRE conformation and enhanced IRP2 binding; and 4) variable IRP1 and IRP2 expression i
79 rivation reduces the RNA-binding activity of IRP2 but not IRP2-C512S or IRP2-C516S, consistent with t
81 ssed in breast cancer, the overexpression of IRP2, but not IRP1, is associated with decreased ferriti
83 PMA stimulated phosphorylation of IRP1 and IRP2 by at least 2-3-fold without affecting incorporatio
86 esis and thiol modification show that, while IRP2 C512 and C516 do not directly interact with RNA, bo
88 ces the RNA-binding activity of IRP2 but not IRP2-C512S or IRP2-C516S, consistent with the formation
89 nding activity of IRP2 but not IRP2-C512S or IRP2-C516S, consistent with the formation of a disulfide
90 ferritin or TfR expression by iron and that IRP2 can act as the sole IRE-dependent mediator of cellu
92 D), in virulence gene profiles (fyuA, irp1, irp2, chuA, fepC, ibeA, kpsMII, iss), in having a larger
93 -fold in rabbit reticulocyte lysates (IRP1 + IRP2), confirming differences in IRP2 binding observed f
94 obis(2-nitrobenzoic acid) (DTNB), indicating IRP2 contains a cysteine(s) that is (are) necessary for
95 IREs) and iron-regulatory proteins (IRP1 and IRP2), controlling either mRNA translation or stability.
96 ith iron-regulatory protein-1 (IRP1) whereas IRP2 controls the mRNAs encoding the L- and H-subunits o
98 tion of iron regulatory protein 1 (IRP1) and IRP2 coordinate the use of messenger RNA-encoding protei
102 for IRP2, which allowed study of endogenous IRP2 degradation in HEK293A cells under more physiologic
105 ulated by a proteolytic pathway that couples IRP2 degradation to intracellular iron levels through th
109 (EPO) overproduction, whereas those who lack IRP2 develop microcytic anemia, believed to result from
113 data show that reversible phosphorylation of IRP2 during G(2)/M has a role in modulating the iron-ind
115 in activity and expression of both IRP1 and IRP2 during phorbol 12-myristate 13-acetate (PMA)-induce
116 There are two identified IRPs, IRP1 and IRP2, each of which binds consensus IREs present in euka
120 anced IRP2 binding; and 4) variable IRP1 and IRP2 expression in human cells and during development (I
121 ith breast cancer demonstrate that increased IRP2 expression is associated with high-grade cancer.
124 ectron microscopy (cryo-EM) structure of the IRP2-FBXL5-SKP1 complex reveals that the cluster organiz
125 itin ligase complex containing FBXL5 targets IRP2 for proteasomal degradation under iron- and oxygen-
128 ity also allows FBXL5 to physically dislodge IRP2 from iron-responsive element RNA to facilitate its
129 ch after striatal ICH, the effect of IRP1 or IRP2 gene knockout on ferritin expression and injury was
130 strains with mutations in either the psn or irp2 gene were avirulent in mice when inoculated subcuta
135 ment (IRE)-binding activity of both IRP1 and IRP2, IFN-gamma treatment decreased IRP2 activity in an
137 icient conditions, the steady-state level of IRP2 in HEK293A cells is regulated by the nonproteasomal
141 he role of NO. in the regulation of IRP1 and IRP2 in rat hepatoma cells was investigated by using the
145 he degradation of iron regulatory protein 2 (IRP2) in iron-replete cells is a key event in this pathw
152 that the region of IRP2 that is involved in IRP2 iron-mediated degradation lies outside of the 73-am
154 These results suggest that dysregulation of IRP2 is an early nodal point underlying altered iron met
156 used previously to study IRP1, we find that IRP2 is degraded in rabbit fibroblast cells exposed to h
157 Because simultaneous knockout of IRP1 and IRP2 is embryonically lethal, it has not been possible t
162 to basal mammalian iron homeostasis, whereas IRP2 is sensitive to iron status and can compensate for
163 e site-specific oxidations in IRP2, oxidized IRP2 is ubiquitinated, and ubiquitinated IRP2 subsequent
168 nvolved in iron metabolism, and the level of IRP2 itself is regulated by varying the rate of its degr
175 e that the disruption of mouse IRP1, but not IRP2, leads to profound HIF2alpha-dependent abnormalitie
176 er, our data indicate that hypoxia increases IRP2 levels by a post-translational mechanism involving
177 rotein 1 (IRP1) was activated, and increased IRP2 levels, indicative of relative cytosolic iron deple
179 , and dysregulation of these proteins due to Irp2 loss causes functional iron deficiency in beta cell
180 or 1 (TfR1) expression, whereas knockdown of IRP2 marginally affected IRE binding activity but caused
181 rted in iron regulatory protein 2-deficient (IRP2 -/-) mice coinciding with increased ferritin levels
184 ounced increase in non-heme iron was seen in IRP2-/- mice between 6 and 12 weeks of age, stemming fro
185 TfR expression in erythroid precursors of IRP2-/- mice is reduced, and bone marrow iron stores are
186 f IRP1 greatly exceeds that of IRP2, whereas IRP2-/- mice misregulate the expression of target protei
187 tem, evidence of abnormal iron metabolism in IRP2-/- mice precedes the development of adult-onset pro
189 egulate expression of the same target genes, IRP2-/- mice significantly misregulate iron metabolism a
191 Third, the Ba/F3 family of cells express IRP2 mRNA at a level similar to other murine cell lines,
195 synthesis of Psn and proteins encoded by the irp2 operon as well as decreased expression from the psn
198 5 plays a critical role in limiting IRP1 and IRP2 overaccumulation when cytosolic Fe-S cluster assemb
200 lity to catalyze site-specific oxidations in IRP2, oxidized IRP2 is ubiquitinated, and ubiquitinated
201 esence of aap (P = 0.004), astA (P = 0.001), irp2 (P = 0.0006), pet (P = 0.002), and set1A (P = 0.014
206 demonstrate that iron regulatory protein 2 (IRP2) plays a key role in iron accumulation in breast ca
207 -sulfur cluster within FBXL5, which promotes IRP2 polyubiquitination and degradation in response to b
209 wth in cells carrying wild-type p53, loss of IRP2 promoted cell growth in cancer cells expressing mut
210 COPD susceptibility gene and have shown that IRP2 protein is increased in the lungs of individuals wi
214 a-inducible factor 1 (HIF-1), also increases IRP2 protein levels; however, cobalt-induced IRP2 lacks
219 ariations in IRE structure and cellular IRP1/IRP2 ratios can provide a range of finely tuned, mRNA-sp
220 overexpression of iron regulatory protein 2 (IRP2) recapitulates many aspects of the alterations in f
221 on sensing via the FBXL5 hemerythrin domain, IRP2 regulation, and cellular responses to maintain mamm
222 teine residues on iron regulatory protein 2 (IRP2), rendering it unable to repress ferritin mRNA tran
223 ies showed that iron-mediated degradation of IRP2 requires the presence of critical cysteines that re
226 Sequence analysis of the region upstream of irp2 revealed the presence of a gene (ybtA) with homolog
231 degradation, but studies have suggested that IRP2 RNA binding is also regulated by thiol oxidation.
233 er-157 phosphorylation during G(2)/M reduces IRP2 RNA-binding activity and increases ferritin synthes
234 phosphorylation during mitotic exit restores IRP2 RNA-binding activity and represses ferritin synthes
235 t synthesis increase, and a late phase where IRP2 RNA-binding activity increases and iron uptake and
239 rovide insight into the structural basis for IRP2-RNA interactions and reveal an iron-independent mec
241 experiments demonstrated that IRP1, but not IRP2, selectively bound the APP IRE in human neural cell
244 rotein levels were dramatically decreased in Irp2(-/-) spleens, whereas ferrochelatase mRNA levels we
248 Finally, we found that ectopic expression of IRP2 suppressed cell growth in a mutant p53-dependent ma
251 geted deletion of iron regulatory protein 2 (IRP2-/-) that have been reported to develop neurodegener
253 t, upon oxidation, promotes FBXL5 binding to IRP2 to effect its oxygen-dependent degradation, unveili
255 s, iron regulatory protein 1 and 2 (IRP1 and IRP2) to stem loop structures, known as iron-responsive
257 The levels of expression of heme-oxidized IRP2 ubiquitin ligase 1L (HOIL-1L), HOIL-1-interacting p
258 interacting protein (SHARPIN), heme-oxidized IRP2 ubiquitin ligase-1 (HOIL-1), and HOIL-1-interacting
259 ly interact with LUBAC subunit Heme-oxidized IRP2 ubiquitin ligase-1 (HOIL-1L) and conjugate K48-link
264 the biochemical characteristics of IRP1 and IRP2, we expressed wild-type and mutant rat IRP1 and IRP
265 s of multiple IRE interactions with IRP1 and IRP2 were compared between the native TfR-3'-UTR sequenc
266 Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced ex
268 ession level of IRP1 greatly exceeds that of IRP2, whereas IRP2-/- mice misregulate the expression of
269 expression of the iron regulatory protein-2 (IRP2), which increases the intracellular iron pool.
271 utilized a sensitive, quantitative assay for IRP2, which allowed study of endogenous IRP2 degradation
272 ed by the iron regulatory proteins, IRP1 and IRP2, which regulate proteins involved in iron homeostas
273 h the virulence genes aggR, set1A, aatA, and irp2, which were found in 16 (40%), 17 (43%), 10 (25%),
274 on of the iron regulatory proteins (IRP1 and IRP2) with canonical IREs controls iron-dependent transl
275 lays only a minor role in the degradation of IRP2, with almost all the IRP2 being degraded by a nonpr