ライフサイエンスコーパス: prolyl hydroxylase

1 YRK1B) requires prolyl hydroxylation by PHD1 prolyl hydroxylase.

2 members, Phd2 appears to be the primary HIF prolyl hydroxylase.

3 , but is not present in bacteria, which lack prolyl hydroxylase.

4 which is related to hypoxia-inducible factor prolyl hydroxylases.

5 S)-2HG, but not (R)-2HG, to inhibit the EglN prolyl hydroxylases.

6 ted for degradation via hydroxylation by HIF-prolyl hydroxylases.

7 nteracts with both HIF-1alpha and HIF-1alpha prolyl hydroxylases.

8 otein to counteract any residual activity of prolyl hydroxylases.

9 We demonstrate that a combination of prolyl hydroxylase 1 and factor inhibiting HIF hydroxyla

10 hydroxylation and form complexes with either prolyl hydroxylase 1 or factor inhibiting HIF.

11 The human hypoxia-inducible factor prolyl hydroxylases 1, 2, and 3 (HIF-PHD1, -2, and -3) a

12 and (3beta-adiol)-dependent transcription of prolyl hydroxylase 2 (PHD2) also known as Egl nine homol

13 be a mouse line with conditional loss of HIF prolyl hydroxylase 2 (PHD2) in very early hematopoietic

14 The human hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) readily crystallises as a ho

15 se mutation in the EGLN1 gene, which encodes prolyl hydroxylase 2 (PHD2), that contributes to this ad

16 (HIF-1alpha), proliferation and upregulation prolyl hydroxylase 2 (PHD2), the enzyme which prevents a

17 es the HIF (hypoxia-inducible factor)/PHD-2 (prolyl hydroxylase 2)-constituted oxygen machinery, we h

18 R-199a and is responsible for downregulating prolyl hydroxylase 2, required for stabilization of Hif-

19 A cross with mice deficient in prolyl hydroxylase 2, which hydroxylates hypoxia-inducib

20 enic effects during acute colitis via a NTR1-prolyl hydroxylase 2/HIF-1alpha-miR-210 signaling pathwa

21 Overexpression of prolyl-hydroxylase 2 (PHD2) transgene, a predominant iso

22 Specific knockout of prolyl hydroxylase-2 (PHD2) increased HIF-2alpha/Notch3

23 ible factor-1 alpha is naturally degraded by prolyl hydroxylase-2 (PHD2) protein.

24 8 expression by either transfection with HIF-prolyl hydroxylase-2 small interfering RNA or overexpres

25 oxalylglycine or a small hairpin RNA against prolyl hydroxylase-2, increased both hypoxia-inducible f

26 in augmented S-nitrosation of caspase-3 and prolyl-hydroxylase-2, the enzyme responsible for targeti

27 Interaction of PKM2 with prolyl hydroxylase 3 (PHD3) enhances PKM2 binding to HIF

28 nction, we have shown that MUC1 up-regulates prolyl hydroxylase 3 (PHD3) expression and promotes HIF-

29 Here we report that prolyl hydroxylase 3 (PHD3) interacts with nonmuscle act

30 orter for hypoxia, expressing EGFP driven by prolyl hydroxylase 3 (phd3) promoter/regulatory elements

31 itin ligase Siah2 has been shown to regulate prolyl hydroxylase 3 (PHD3) stability with concomitant e

32 In the canonical HIF signaling pathway, HIF-prolyl hydroxylase 3 (PHD3) suppresses HIF-2alpha protei

33 he ability of Siah2 to target its substrates prolyl hydroxylase 3 and Spry2 (Sprouty2) for ubiquitin-

34 dulate HIF-1alpha degradation by suppressing prolyl hydroxylase 3 expression.

35 , including MMP-3, ADAMTS-5, syndecan 4, and prolyl hydroxylase 3.

36 ) is hydroxylated on proline 419 and 426 via prolyl hydroxylase 3.

37 including specific roles for HIF-1alpha and prolyl hydroxylase-3.

38 ted-like ER kinase pathway by suppression of prolyl hydroxylase 4.

39 Inhibition of PHD3 prolyl hydroxylase activity by dimethyloxalylglycine als

40 of different HIF target genes to changes in prolyl hydroxylase activity differ, quantitatively and q

41 s a negative regulator of NF-kappaB, and its prolyl hydroxylase activity is required for this effect.

42 ts of Toxoplasma on HIF-1alpha abundance and prolyl hydroxylase activity require activin-like recepto

43 lated DNA substrates, but it did exhibit the prolyl hydroxylase activity that has also been ascribed

44 alpha downregulation was suppressed when HIF-prolyl hydroxylase activity was pharmacologically inhibi

45 ferrioxamine, and hypoxia, all inhibitors of prolyl hydroxylase activity, led to repression of C2C12

46 xygen availability, which is crucial for HIF-prolyl hydroxylase activity.

47 Unexpectedly, we did not detect prolyl-hydroxylase activity on any reported non-HIF prot

48 rbate reversed albumin-induced inhibition of prolyl-hydroxylase activity.

49 ING4 directly associates with the HIF prolyl hydroxylase, an Fe(II)-dependent oxygenase previo

50 ylase domain protein (PHD, also known as HIF prolyl hydroxylase and egg laying-defective nine protein

51 roles such as the regulation of activity of prolyl hydroxylases and adaptive responses to hypoxia.

52 result from fumarate-dependent inhibition of prolyl hydroxylases and subsequent evasion from von Hipp

53 e been previously found to be substrates for prolyl hydroxylases and subsequent O-glycosylation of th

54 ha1 collagen IV by upregulation of alpha(II) prolyl-hydroxylase and increased the release of Arresten

55 D34, fibroblast-specific protein 1,4-hydroxy-prolyl-hydroxylase, and factor XIIIa.

56 esidues in its alpha-subunit, carried out by prolyl-hydroxylases, and subsequent ubiquitination via t

57 Hydroxylase Domain-Containing Protein (PHD) prolyl hydroxylases are oxygen-sensitive enzymes that tr

58 Here we show that responsible prolyl hydroxylases are targets for both nickel(II) and

59 onal progenitor cells and requires the EglN3 prolyl hydroxylase as a downstream effector.

60 ly identified EGLN3, a member of a family of prolyl hydroxylases, as a negative regulator of the NF-k

61 ind to the 2-oxoglutarate site of HIF-1alpha prolyl hydroxylases, but their effects on HIF-1 are not

62 h, we find no evidence ALKBH7 functions as a prolyl-hydroxylase, but we do find Alkbh7(-/-) mice have

63 in addition to regulating HIF stability, HIF prolyl hydroxylases can modulate HIF function through th

64 Either hypoxia or mutations in egl-9, a prolyl hydroxylase cellular oxygen sensor, result in the

65 g pathway through depletion of HIF-targeting prolyl hydroxylase-containing protein 2 (PHD-2) further

66 In mammals, prolyl hydroxylases control levels of the central transc

67 The respective prolyl-hydroxylases (DdPhyA and TgPhyA) catalyze prolyl-

68 TM causes HIF-1alpha downregulation in a HIF-prolyl hydroxylase-dependent manner.

69 The enzymatic activity of prolyl hydroxylases depends on iron as the activating me

70 n mice by injecting 2 structurally unrelated prolyl hydroxylase domain (PHD) enzyme inhibitors: dimet

71 to analyze the expression and regulation of prolyl hydroxylase domain (PHD) enzymes and factor-inhib

72 The oxygen-sensing prolyl hydroxylase domain (PHD) enzymes are key to maint

73 The HIF prolyl hydroxylase domain (PHD) enzymes are non-heme, ir

74 ns, such as iron chelators and inhibitors of prolyl hydroxylase domain (PHD) enzymes, have broad-spec

75 Prolyl hydroxylase domain (PHD) proteins are well recogn

76 Prolyl hydroxylase domain (PHD) proteins catalyze oxygen

77 Prolyl hydroxylase domain (PHD) proteins, including PHD1

78 Prolyl hydroxylase domain (PHD)-2 protein, a major PHD i

79 EK2) stress pathway activation, and enhanced prolyl hydroxylase domain (PHD)-3 (EGLN3) mRNA expressio

80 oxygen concentrations are directly sensed by prolyl hydroxylase domain (PHD)-containing proteins, whi

81 The prolyl hydroxylase domain (PHD)-hypoxia inducible factor

82 In these domain-swapping experiments, prolyl hydroxylase domain 1 (PHD1) and PHD2 preferential

83 Treatment of these mice with Fg4497, a prolyl hydroxylase domain 2 (PHD2) inhibitor, activated

84 Prolyl hydroxylase domain 2 (PHD2) is deemed a primary o

85 Prolyl hydroxylase domain 2 (PHD2) plays an important ro

86 AM features, cancer cells were inoculated in prolyl hydroxylase domain 2 (PHD2)-haplodeficient mice,

87 protein, increased HIF-1alpha, and decreased prolyl hydroxylase domain 2 in nuclear fractions, which

88 that 2-hydroxyglutarate-enabled catalysis by prolyl hydroxylase domain 2 is not enantiomer-specific a

89 tion of 2-oxoglutarate oxygenases, including prolyl hydroxylase domain 2, the most important human pr

90 ue, affecting HIF2alpha interaction with the prolyl hydroxylase domain 2-containing protein, decreasi

91 lization of HIF-2alpha using an inhibitor of prolyl hydroxylase domain 3 (an upstream inhibitor of HI

92 Treatment of macrophages with the prolyl hydroxylase domain 3 inhibitor AKB-6899 stabilize

93 Cofactors involved in prolyl hydroxylase domain activity were increased in PAH

94 through its interaction with the O2-sensing prolyl hydroxylase domain containing protein EGLN3 (or P

95 ble factor (HIF) by a set of closely related prolyl hydroxylase domain enzymes (PHD1, 2 and 3) regula

96 The HIF prolyl hydroxylase domain enzymes (PHDs) are Fe(II)- and

97 factor) and its regulatory hydroxylases, the prolyl hydroxylase domain enzymes (PHDs).

98 ng the activity of iron-dependent intestinal prolyl hydroxylase domain enzymes.

99 We show that loss of the prolyl hydroxylase domain isoform 1 oxygen sensor in mic

100 nchymal pluripotent stem cells revealed that prolyl hydroxylase domain protein (PHD) levels significa

101 In this pathway, prolyl hydroxylase domain protein (PHD) site-specificall

102 en-dependent control of red cell mass is the prolyl hydroxylase domain protein (PHD):hypoxia inducibl

103 Under normoxic conditions, prolyl hydroxylase domain protein (PHD, also known as HI

104 Prolyl hydroxylase domain protein 2 (PHD2) (also known a

105 Prolyl hydroxylase domain protein 2 (PHD2) belongs to an

106 Prolyl hydroxylase domain protein 2 (PHD2) is a cellular

107 Here we show that prolyl hydroxylase domain protein 2 (PHD2), an enzyme mo

108 gene, which encodes for HIF-2alpha, and the prolyl hydroxylase domain protein 2 (PHD2, also known as

109 Prolyl hydroxylase domain protein 2 (PHD2, also known as

110 Tibetans bear a genetic signature in the prolyl hydroxylase domain protein 2 (PHD2/EGLN1) gene, w

111 ed with lentiviral short hairpin RNA against prolyl hydroxylase domain protein 2 (shPHD2) to silence

112 K2), associated with and was hydroxylated by prolyl hydroxylase domain protein 3 (PHD3).

113 ay for controlling red cell mass is the PHD (prolyl hydroxylase domain protein):hypoxia-inducible fac

114 Prolyl hydroxylase domain proteins (PHD isozymes 1-3) re

115 demonstrate that silencing and expression of prolyl hydroxylase domain proteins (PHD1-3) increase and

116 al inhibition of a class of enzymes known as prolyl hydroxylase domain proteins (PHDs) has neuroprote

117 Deficiencies in prolyl hydroxylase domain proteins (PHDs) may lead to th

118 Hypoxia-inducible factor (HIF) prolyl hydroxylase domain proteins (PHDs) serve as oxyge

119 Oxygen sensing is mediated by prolyl hydroxylase domain proteins (PHDs), which use O(2

120 Prolyl hydroxylase domain proteins hydroxylate substrate

121 PHD1, PHD2, and PHD3 are prolyl hydroxylase domain proteins that regulate the sta

122 srupt the hydroxylation domain recognized by prolyl hydroxylase domain-2 containing protein, leading

123 l and biophysical studies on the reaction of prolyl hydroxylase domain-containing enzyme (PHD) isofor

124 While canonically regulated by prolyl hydroxylase domain-containing enzymes (PHDs), the

125 Pharmacological inhibitors of prolyl hydroxylase domain-containing enzymes (PHDs), whi

126 The Prolyl Hydroxylase Domain-Containing Protein (PHD) proly

127 We recently demonstrated that Prolyl Hydroxylase Domain-containing Protein 2 (Phd2) is

128 found that knockout of EGLN1, which encodes prolyl hydroxylase domain-containing protein 2 (PHD2), r

129 1alpha) and Hif-2alpha is regulated by three prolyl hydroxylase domain-containing protein isoforms (P

130 a and -2alpha, respectively) via blockade of prolyl hydroxylase domain-containing proteins (HIF-PHDs)

131 ia-inducible factors (HIFs) by inhibition of prolyl hydroxylase domain-containing proteins (PHDs) is

132 6 that binds the human oxygen sensing enzyme prolyl-hydroxylase domain containing protein (PHD)2 and

133 ographic analyses revealing that Pseudomonas prolyl-hydroxylase domain containing protein (PPHD) cont

134 eudomonas aeruginosa lacking the Pseudomonas prolyl-hydroxylase domain-containing protein, which has

135 s lacking the hypoxia response component and prolyl hydroxylase egl-9, with impaired subcellular loca

136 Three HIF prolyl hydroxylases (EGLN1, EGLN2, and EGLN3) have been

137 The three EglN prolyl hydroxylases (EglN1, EglN2, and EglN3) regulate t

138 ulatory feedback loop involving the HIFalpha prolyl hydroxylase, Egln3.

139 , we have identified a critical role for the prolyl hydroxylase enzyme Phd2 in maintaining the balanc

140 hypoxia-inducible transcription factor (HIF)-prolyl hydroxylase enzymes (PHD1, PHD2, and PHD3) is a s

141 Prolyl hydroxylase enzymes (PHD1-3) are molecular oxygen

142 Prolyl hydroxylase enzymes (PHDs) sense cellular oxygen

143 the cytosol, where they inhibit a family of prolyl hydroxylase enzymes (PHDs).

144 The EGLN (also called PHD) prolyl hydroxylase enzymes and their canonical targets,

145 The HIF prolyl hydroxylase enzymes PHD1, PHD2 and PHD3 regulate

146 Cells rely on prolyl hydroxylase enzymes to sense low levels of oxygen

147 nts that activate HIF, via inhibition of the prolyl hydroxylase enzymes, might be developed to induce

148 indicating an inhibition of the activity of prolyl-hydroxylases, enzymes promoting the degradation o

149 nes, is stabilized via regulation by Ofd1, a prolyl hydroxylase family member inhibited by hypoxia, a

150 the pharmacological manipulation of the HIF prolyl hydroxylase for ischemic diseases.

151 y decreases PHD2 abundance, which is the key prolyl hydroxylase for regulating HIF-1alpha.

152 Recently, mutations in the prolyl hydroxylase gene (PHD) 1 and 2 and in the hypoxia

153 EGLN3, a member of the EGLN family of prolyl hydroxylases, has been shown to catalyze hydroxyl

154 pha a plausible mechanism, inhibition of HIF prolyl hydroxylases, has previously been suggested by in

155 The egg-laying abnormal-9 (EGLN) prolyl hydroxylases have been shown to regulate the stab

156 is degraded under normoxic conditions by HIF-prolyl hydroxylase (HIF-PHD).

157 elease erythropoietin under hypoxia, via the prolyl hydroxylase-HIF-2alpha axis, in the human kidney.

158 Hif-1 prolyl hydroxylase (Hph), another effector of CycD/Cdk4,

159 coding transcription/translation regulators, prolyl hydroxylases, hybrid cluster proteins, proteases,

160 hat the expression of the EGLN3-encoded PHD3 prolyl hydroxylase identifies proinflammatory macrophage

161 called Egln1) appears to be the primary HIF prolyl hydroxylase in cell culture experiments.

162 ffects of 2-hydroxyglutarate on catalysis by prolyl hydroxylases in vitro and suggest that non-enzyma

163 The roles of 2-oxoglutarate (2OG)-dependent prolyl-hydroxylases in eukaryotes include collagen stabi

164 Prolyl hydroxylase inhibition also potently suppressed m

165 inducible factor (HIF) stabilization via HIF prolyl hydroxylase inhibition using the isoquinolone Rox

166 cologic or genetic activation of HIF via HIF prolyl-hydroxylase inhibition protected wild-type animal

167 Indeed, HIF1alpha activation by a prolyl hydroxylase inhibitor (PHI) synergizes with gluco

168 n inhibitor (pevonedistat [MLN-4924]), and a prolyl hydroxylase inhibitor (roxadustat [FG-4592]).

169 odels, augmenting HIF-1alpha levels with the prolyl hydroxylase inhibitor 2-(1-chloro-4-hydroxyisoqui

170 the addition of proteasome inhibitors or the prolyl hydroxylase inhibitor 2-hydroxyglutarate, and bea

171 al cancer cell lines, was insensitive to the prolyl hydroxylase inhibitor dimethyloxaloyl glycine, an

172 We used the prolyl hydroxylase inhibitor ethyl-3,4-dihydroxybenzoate

173 One such agent, the HIF prolyl hydroxylase inhibitor FG-4383, was active in the

174 zation of hypoxia inducible factors with the prolyl hydroxylase inhibitor FG-4497 did not influence I

175 een the dose of the hypoxia-inducible factor-prolyl hydroxylase inhibitor GSK1278863 and hemoglobin r

176 Systemic administration of a HIF-prolyl hydroxylase inhibitor replicated the Phd2-deficie

177 bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated e

178 and show that ethyl 3,4-dihydroxybenzoate, a prolyl hydroxylase inhibitor, decreases tumor fibrosis a

179 d the effect of systemic administration of a prolyl hydroxylase inhibitor, dimethyloxalylglycine, in

180 ls lacking MIF are defective in hypoxia- and prolyl hydroxylase inhibitor-induced HIF-1alpha stabiliz

181 To determine whether antenatal or postnatal prolyl-hydroxylase inhibitor (PHi) therapy increases lun

182 us transection=ALPPS) or the addition of the prolyl-hydroxylase inhibitor dimethyloxalylglycine (DMOG

183 ent study, we report the discovery of an HIF prolyl-hydroxylase inhibitor, DMOG [N-(2-Methoxy-2-oxoac

184 this phase 1 study, we used an orally active prolyl-hydroxylase inhibitor, FG-2216, to stabilize HIF

185 protective effects were not observed in HIF prolyl-hydroxylase inhibitor-treated animals lacking end

186 Prolyl hydroxylase inhibitors (PHI) promote stabilizatio

187 Several HIF-prolyl hydroxylase inhibitors (PHIs) induced erythropoie

188 -2alpha in the neuroprotective mechanisms of prolyl hydroxylase inhibitors and in an endogenous cell

189 Presently used prolyl hydroxylase inhibitors are lipophilic 2-oxoglutar

190 ions for the development of paralog-specific prolyl hydroxylase inhibitors as therapeutic agents.

191 dition to exhibiting pro-angiogenic effects, prolyl hydroxylase inhibitors can modulate the plasminog

192 The prolyl hydroxylase inhibitors ethyl 3,4-dihydroxybenzoic

193 rovides rationale for the therapeutic use of prolyl hydroxylase inhibitors in the setting of acute or

194 To investigate whether prolyl hydroxylase inhibitors modulate the net plasminog

195 This study assesses the effect of prolyl hydroxylase inhibitors on plasminogen activation

196 IF-1alpha overexpression or HIF accumulating prolyl hydroxylase inhibitors reduced ErbB4 endocytosis,

197 Accordingly, HIF prolyl hydroxylase inhibitors stabilize HIF and stimulat

198 Hypoxia-inducible factor prolyl hydroxylase inhibitors stabilize levels of hypoxi

199 The use of prolyl hydroxylase inhibitors such as l-mimosine (L-MIM)

200 al of novel therapies such as ascorbic acid, prolyl hydroxylase inhibitors, activin traps, hepcidin,

201 abilization achieved by using small-molecule prolyl-hydroxylase inhibitors reduced M-MITF expression,

202 e.g. screens of the hypoxia-inducible factor prolyl-hydroxylase inhibitors revealed that vadadustat i

203 The EglN2/PHD1 prolyl hydroxylase is an important oxygen sensor contrib

204 lyl 4-hydroxylase related to animal HIFalpha prolyl hydroxylases is required for optimal parasite pro

205 droxylase domain 2, the most important human prolyl hydroxylase isoform.

206 lycerate kinase 1 and Glucokinase but not of prolyl hydroxylase isoforms.

207 ver-specific deletions of genes encoding HIF-prolyl-hydroxylase isoforms (PHD1, PHD2, and PHD3) that

208 particularly, hypoxia-inducible factor (HIF) prolyl hydroxylases, JmjC domain-containing histone deme

209 l nervous system, inhibition of collagen and prolyl hydroxylases lead to altered microenvironment and

210 Thus, prolyl hydroxylase mediated hydroxylation and subsequent

211 ion in ischemic tissues because of increased prolyl hydroxylase-mediated hydroxylation (P<0.05) and p

212 lish the prognostic significance of collagen prolyl hydroxylase mRNA expression in human breast cance

213 phages, increasing HIF-1alpha and decreasing prolyl hydroxylase mRNA production in a TLR4-dependent f

214 When oxygen is present, the prolyl hydroxylase Ofd1 down-regulates Sre1N activity in

215 ereas over-expression of hph (Drosophila HIF prolyl hydroxylase) only accelerated BCM.

216 radation of HIF-2alpha whereas inhibitors of prolyl hydroxylases or proteosome were ineffective.

217 ses succinate availability to regulate HIF-1 prolyl hydroxylases, or stimulates mitochondrial reactiv

218 nactivation or pharmacological inhibition of prolyl hydroxylase oxygen sensors, indicating the molecu

219 er myogenic potential of MDSPCs derived from prolyl hydroxylase (Phd) 3-knockout (Phd3(-/-)) mice, wh

220 alpha is rapidly degraded by 2 hydroxylases: prolyl hydroxylase (PHD) and factor-inhibiting HIF-1 (FI

221 Therefore, HIF prolyl hydroxylase (PHD) enzymatic activity is critical

222 inactivation of the critical oxygen-sensing prolyl hydroxylase (PHD) enzymes (PHD1-3) in osteoprogen

223 The hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) enzymes represent novel targets

224 rest in the development of inhibitors of the prolyl hydroxylase (PHD) enzymes that regulate the hypox

225 al effects of cellular hypoxia are sensed by prolyl hydroxylase (PHD) enzymes which regulate HIFs.

226 regulated by the 2-oxoglutarate and Iron(II) prolyl hydroxylase (PHD) enzymes, which hydroxylate the

227 a structural class of pan-inhibitors of the prolyl hydroxylase (PHD) family of enzymes for the treat

228 ermore, eEF2 phosphorylation was mimicked by prolyl hydroxylase (PHD) inhibition with dimethyloxalylg

229 For these purposes, we used a novel prolyl hydroxylase (PHD) inhibitor (FG-4497) that readil

230 Inhibition of prolyl hydroxylase (PHD) is known to activate the transc

231 ecent studies suggest a differential role of prolyl hydroxylase (PHD) isoforms in controlling hypoxia

232 We postulated that the well described prolyl hydroxylase (PHD) oxygen sensors and HIF negative

233 ts substrates as part of an oxygen-dependent prolyl hydroxylase (PHD) reaction, with hypoxia-inducibl

234 ical prevention of HIF-1alpha degradation by prolyl hydroxylase (PHD) under normoxic conditions is em

235 ion of the HIF-1alpha subunit is mediated by prolyl hydroxylase (PHD), the von Hippel-Lindau (VHL)/El

236 The role of prolyl hydroxylase (PHD)-3 as a hypoxia inducible factor

237 of which, when in excess, inhibits HIFalpha prolyl hydroxylase (PHD).

238 ndergoes oxygen-dependent degradation by the prolyl hydroxylase (PHD)/von Hippel-Lindau (VHL) system.

239 CODD) of HIFalpha isoforms, as catalysed by prolyl hydroxylases (PHD 1-3).

240 athway, Siah1, and Siah2, and suppressed the prolyl hydroxylases (PHD) 2 and PHD3.

241 te-specific hydroxylation carried out by HIF prolyl hydroxylases (PHD) and subsequent proteasomal deg

242 fects of five hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD) inhibitors on PC12 cells and p

243 inhibitors of hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD) is described.

244 nhibitors of the iron-dependent enzyme class prolyl hydroxylases (PHD), which target alpha subunits o

245 poxia-inducible factor-1alpha (HIF-alpha) by prolyl hydroxylases (PHD).

246 tor (HIF-1alpha) is rapidly degraded via the prolyl hydroxylases (PHD)/VHL pathways.

247 The discovery of the HIF prolyl-hydroxylase (PHD) enzymes as oxygen sensors raise

248 l-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintai

249 stimulated in normoxia by the oxygen-sensing prolyl hydroxylase PHD1 (also known as EGLN2).

250 le factor (HIF), which is inhibited by three prolyl hydroxylases (PHD1, PHD2, and PHD3).

251 In humans, they comprise three prolyl hydroxylases (PHD1-3 or EGLN1-3) and factor inhib

252 hydroxylases; in humans there are three HIF prolyl hydroxylases (PHD1-3) and an asparaginyl hydroxyl

253 tivity are regulated by the oxygen-sensitive prolyl hydroxylases (PHD1-3), but the role of PHDs in ne

254 The prolyl-hydroxylases (PHD1/2/3) and the asparaginyl-hydro

255 Egln-9-type prolyl hydroxylases, PHD1 and PHD2, coimmunoprecipitated

256 ression of the three most well characterized prolyl-hydroxylases, PHD1, PHD2, and PHD3, and the expre

257 oxylation of HIF-1alpha or HIF-2alpha by the prolyl hydroxylase PHD2 is required for binding of the v

258 ependent on expression of the oxygen-sensing prolyl hydroxylase PHD2.

259 in vitro did not inhibit the activity of the prolyl-hydroxylase PHD2, experiments with mouse liver sh

260 5 is a novel binding partner of the main HIF-prolyl hydroxylase, PHD2, but not of PHD1 or PHD3.

261 that are heterozygous for the principal HIF prolyl hydroxylase, PHD2, show enhanced ventilatory sens

262 Here we show that the prolyl hydroxylase PHD3 restrains tumour growth in respo

263 We report in this study that the prolyl hydroxylase PHD3-encoding EGLN3 gene is specifica

264 Hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are alpha-ketoglutarate (alph

265 ting evidence suggests that oxygen-sensitive prolyl hydroxylases (PHDs) are important regulators of t

266 Prolyl hydroxylases (PHDs) are oxygen sensors that stabi

267 Prolyl hydroxylases (PHDs) perceive intracellular oxygen

268 uitin ligase as well as the oxygen-sensitive prolyl hydroxylases (PHDs) represent essential regulator

269 tion factor HIF-1alpha relies on a family of prolyl hydroxylases (PHDs) that hydroxylate hypoxia-indu

270 e response to chronic hypoxia is mediated by prolyl hydroxylases (PHDs) that regulate the levels of h

271 er normoxia but stabilized when O2-dependent prolyl hydroxylases (PHDs) that target its O2-dependent

272 ine residues are hydroxylated by a family of prolyl hydroxylases (PHDs).

273 mselves controlled by the oxygen-sensing HIF prolyl hydroxylases (PHDs).

274 induction involves succinate, which inhibits prolyl hydroxylases (PHDs).

275 ver, bioinformatics imply that 2OG-dependent prolyl-hydroxylases (PHDs) homologous to those acting as

276 The PHD family of oxygen-dependent prolyl hydroxylases plays a pivotal role in regulating H

277 le of the putative oxygen sensor Pseudomonas prolyl hydroxylase (PPHD) in the control of virulence an

278 We show that expression of collagen prolyl hydroxylases promotes cancer cell alignment along

279 e conclude that the oxygen dependence of the prolyl hydroxylase reaction is sufficient to mediate HIF

280 tion factor HIF-alpha and its oxygen-sensing prolyl hydroxylase repressor, EGLN Despite this loss, ph

281 Prolyl hydroxylases require oxygen as a substrate, and t

282 by mutations in its negative regulator egl-9/prolyl hydroxylase shifts behavioral oxygen preferences

283 ver, under hypoxic conditions, inhibition of prolyl hydroxylase significantly increased erythropoieti

284 emically delivered siRNAs targeting the EglN prolyl hydroxylases specifically in the liver, leading t

285 Here we show that OGFOD1 is a prolyl hydroxylase that catalyzes the posttranslational

286 protein ubiquitin ligases, is modified by a prolyl hydroxylase that mediates O(2) regulation of the

287 -independent manner, expression of the EGLN1 prolyl hydroxylase that regulates HIF-1alpha degradation

288 PCBP2 are required for iron delivery to the prolyl hydroxylase that regulates HIF1.

289 the transcription of genes encoding collagen prolyl hydroxylases that are critical for collagen depos

290 Because the prolyl hydroxylases that regulate HIF stability are oxyg

291 Inhibition of prolyl hydroxylases that regulate the degradation of hyp

292 expression, could be mimicked by inhibiting prolyl-hydroxylases that activate HIF1, suggesting that

293 EglN1, the main HIFalpha prolyl-hydroxylase, undergoes oxidative self-inactivatio

294 Inhibition of prolyl hydroxylases, using either dimethyloxalylglycine

295 o-substrate for the hypoxia-inducible factor prolyl hydroxylases via enzyme-catalysed oxidation to 2-

296 ion of the HIF-1alpha subunit is mediated by prolyl hydroxylase, von Hippel-Lindau protein (VHL)/Elon

297 he degradation of HIF-1alpha is regulated by prolyl hydroxylases, we examined the effect of systemic

298 r (HIF) and 2-HG is a known inhibitor of HIF prolyl hydroxylases, we hypothesized that 2-HG may be re

299 are responsible for the interaction with HIF-prolyl hydroxylase, were deleted.

300 The work identifies a human prolyl hydroxylase with a role in translational regulati