PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34781297-2 2021 In addition, the oxygen-dependent conversion of HIF-1alpha in nucleus pulposus cells is controlled by the protein Proline 4-hydroxylase domain (PHD) family. Proline 114-121 hypoxia inducible factor 1 subunit alpha Homo sapiens 48-58 26997627-4 2016 The oxygen-sensing PHDs regulate the stability of hypoxia-inducible factor 1alpha (HIF1alpha) as well as other proline-containing proteins by catalyzing the hydroxylation of proline residues. Proline 111-118 hypoxia inducible factor 1 subunit alpha Homo sapiens 50-81 26997627-4 2016 The oxygen-sensing PHDs regulate the stability of hypoxia-inducible factor 1alpha (HIF1alpha) as well as other proline-containing proteins by catalyzing the hydroxylation of proline residues. Proline 111-118 hypoxia inducible factor 1 subunit alpha Homo sapiens 83-92 26997627-4 2016 The oxygen-sensing PHDs regulate the stability of hypoxia-inducible factor 1alpha (HIF1alpha) as well as other proline-containing proteins by catalyzing the hydroxylation of proline residues. Proline 174-181 hypoxia inducible factor 1 subunit alpha Homo sapiens 50-81 26997627-4 2016 The oxygen-sensing PHDs regulate the stability of hypoxia-inducible factor 1alpha (HIF1alpha) as well as other proline-containing proteins by catalyzing the hydroxylation of proline residues. Proline 174-181 hypoxia inducible factor 1 subunit alpha Homo sapiens 83-92 26628999-4 2015 We also found that vitamin C could increase the proline hydroxylation of HIF-1alpha and reduce the activity of HIF-1alpha. Proline 48-55 hypoxia inducible factor 1 subunit alpha Homo sapiens 73-83 26628999-6 2015 Overexpression of wild-type HIF-1alpha or proline-mutant HIF-1alpha was found to increase the proliferation and migration of human lens epithelial cells. Proline 42-49 hypoxia inducible factor 1 subunit alpha Homo sapiens 57-67 34943229-11 2021 Moreover, lack of free proline (known to upregulate the transcriptional activity of hypoxia-inducible factor 1, HIF-1) contributes to downregulation of HIF-1-dependent pro-survival activity. Proline 23-30 hypoxia inducible factor 1 subunit alpha Homo sapiens 112-117 34943229-11 2021 Moreover, lack of free proline (known to upregulate the transcriptional activity of hypoxia-inducible factor 1, HIF-1) contributes to downregulation of HIF-1-dependent pro-survival activity. Proline 23-30 hypoxia inducible factor 1 subunit alpha Homo sapiens 152-157 32256584-6 2020 HIF-1 signaling pathway modulating P-glycoproteins expression, PI3K-Akt pathway regulating survivin expression, and oxidative phosphorylation were upregulated, while arginine and proline metabolism regulating NO production and glycolysis/gluconeogenesis were downregulated during osimertinib resistance. Proline 179-186 hypoxia inducible factor 1 subunit alpha Homo sapiens 0-5 34537235-2 2021 The principal step in this critical cellular process is the hydroxylation of either or both of the two conserved proline residues P402 and P564 within the oxygen-dependent degradation domain (ODD) of HIF-1alpha subunit via prolyl hydroxylases, which is necessary for binding VHL. Proline 113-120 hypoxia inducible factor 1 subunit alpha Homo sapiens 200-210 32377733-7 2020 The proline hydroxylation of HIF-1alpha by prolyl hydroxylases (PHDs) was previously discovered to be responsible for the rapid degradation of HIF-1alpha. Proline 4-11 hypoxia inducible factor 1 subunit alpha Homo sapiens 29-39 32377733-7 2020 The proline hydroxylation of HIF-1alpha by prolyl hydroxylases (PHDs) was previously discovered to be responsible for the rapid degradation of HIF-1alpha. Proline 4-11 hypoxia inducible factor 1 subunit alpha Homo sapiens 143-153 35415275-6 2022 Heterodimeric HIF transcription factor activity is regulated post-translationally by selective PHD proline hydroxylation of its HIF1alpha subunit, accelerating HIF1alpha ubiquitination and proteasomal degradation, preventing HIF heterodimer assembly, nuclear accumulation, and activation of its target oxygen homeostasis genes. Proline 99-106 hypoxia inducible factor 1 subunit alpha Homo sapiens 128-137 35415275-6 2022 Heterodimeric HIF transcription factor activity is regulated post-translationally by selective PHD proline hydroxylation of its HIF1alpha subunit, accelerating HIF1alpha ubiquitination and proteasomal degradation, preventing HIF heterodimer assembly, nuclear accumulation, and activation of its target oxygen homeostasis genes. Proline 99-106 hypoxia inducible factor 1 subunit alpha Homo sapiens 160-169 28526934-0 2017 Exogenous proline stimulates type I collagen and HIF-1alpha expression and the process is attenuated by glutamine in human skin fibroblasts. Proline 10-17 hypoxia inducible factor 1 subunit alpha Homo sapiens 49-59 30796332-6 2019 MAC inhibited the hydroxylation of HIF-1alpha at the proline 564 residue, while it was reversed by ascorbate. Proline 53-60 hypoxia inducible factor 1 subunit alpha Homo sapiens 35-45 30367042-3 2018 By modulating alpha ketoglutarate (alpha-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1alpha, enhancing its stability in cancer cells. Proline 91-98 hypoxia inducible factor 1 subunit alpha Homo sapiens 116-153 29084919-9 2018 Finally, inhibition of proline biosynthesis significantly enhanced cytotoxicity of sorafenib in vitro and in vivoConclusions: Our results demonstrate that hypoxic microenvironment activates proline metabolism, resulting in accumulation of hydroxyproline that promotes HCC tumor progression and sorafenib resistance through modulating HIF1alpha. Proline 23-30 hypoxia inducible factor 1 subunit alpha Homo sapiens 334-343 29084919-9 2018 Finally, inhibition of proline biosynthesis significantly enhanced cytotoxicity of sorafenib in vitro and in vivoConclusions: Our results demonstrate that hypoxic microenvironment activates proline metabolism, resulting in accumulation of hydroxyproline that promotes HCC tumor progression and sorafenib resistance through modulating HIF1alpha. Proline 190-197 hypoxia inducible factor 1 subunit alpha Homo sapiens 334-343 29037142-6 2017 Using this novel approach, no PHD3 activity toward HIF3 was demonstrated, indirectly pointing to the hydroxylation of the second proline in 564PYIP567 (HIF1) catalyzed by this isozyme. Proline 129-136 hypoxia inducible factor 1 subunit alpha Homo sapiens 152-156 31413262-2 2019 Prolyl hydroxylase 2 (PHD2) dominantly hydroxylates two highly conserved proline residues of HIF-1alpha to promote its degradation. Proline 73-80 hypoxia inducible factor 1 subunit alpha Homo sapiens 93-103 29961792-0 2018 Proline hydroxylation at different sites in hypoxia-inducible factor 1alpha modulates its interactions with the von Hippel-Lindau tumor suppressor protein. Proline 0-7 hypoxia inducible factor 1 subunit alpha Homo sapiens 44-75 29568391-6 2018 In these cells, glycyl-proline (GlyPro, substrate for prolidase) further inhibited DNA and collagen biosynthesis, maintained high prolidase activity, intracellular concentration of proline and up-regulated HIF-1alpha, AMPK, Atg7 and Beclin-1, compared to GlyPro-treated MCF-7 cells. Proline 23-30 hypoxia inducible factor 1 subunit alpha Homo sapiens 206-216 27598034-8 2016 Alternatively, 15d-PGJ2 was found to covalently bind to HIF-1alpha prolyl-4-hydroxylase 2 (PHD2) in MCF-7 cells, which hampers the proline hydroxylation of HIF-1alpha, thereby disrupting ubiquitin-dependent proteasomal degradation of this transcription factor. Proline 131-138 hypoxia inducible factor 1 subunit alpha Homo sapiens 56-66 23542169-7 2014 In addition, RUNX3 directly interacted with the C-terminal activation domain of HIF-1alpha and prolyl hydroxylase (PHD) 2 and enhanced the interaction between HIF-1alpha and PHD2, which potentiated proline hydroxylation and promoted the degradation of HIF-1alpha. Proline 198-205 hypoxia inducible factor 1 subunit alpha Homo sapiens 80-90 26757928-4 2016 The functional consequence of HIF-1alpha methylation is the modulation of HIF-1alpha stability primarily in the nucleus, independent of its proline hydroxylation, during long-term hypoxic and normoxic conditions. Proline 140-147 hypoxia inducible factor 1 subunit alpha Homo sapiens 30-40 26600509-4 2015 C/T single nucleotide polymorphisms were detected at the site of 1285 bp of the HIF-1alpha exon, from a proline to a serine (Pro582Ser). Proline 104-111 hypoxia inducible factor 1 subunit alpha Homo sapiens 80-90 26574473-3 2015 The binding of HIFalpha for VCB is increased by ~1000-fold upon addition of a single hydroxyl group to either of two conserved proline-residues. Proline 127-134 hypoxia inducible factor 1 subunit alpha Homo sapiens 15-23 23542169-7 2014 In addition, RUNX3 directly interacted with the C-terminal activation domain of HIF-1alpha and prolyl hydroxylase (PHD) 2 and enhanced the interaction between HIF-1alpha and PHD2, which potentiated proline hydroxylation and promoted the degradation of HIF-1alpha. Proline 198-205 hypoxia inducible factor 1 subunit alpha Homo sapiens 159-169 23542169-7 2014 In addition, RUNX3 directly interacted with the C-terminal activation domain of HIF-1alpha and prolyl hydroxylase (PHD) 2 and enhanced the interaction between HIF-1alpha and PHD2, which potentiated proline hydroxylation and promoted the degradation of HIF-1alpha. Proline 198-205 hypoxia inducible factor 1 subunit alpha Homo sapiens 159-169 23542169-9 2014 Taken together, these results suggest that RUNX3 destabilizes HIF-1alpha protein by promoting the proline hydroxylation of HIF-1alpha through binding to HIF-1alpha/PHD2. Proline 98-105 hypoxia inducible factor 1 subunit alpha Homo sapiens 62-72 23542169-9 2014 Taken together, these results suggest that RUNX3 destabilizes HIF-1alpha protein by promoting the proline hydroxylation of HIF-1alpha through binding to HIF-1alpha/PHD2. Proline 98-105 hypoxia inducible factor 1 subunit alpha Homo sapiens 123-133 23542169-9 2014 Taken together, these results suggest that RUNX3 destabilizes HIF-1alpha protein by promoting the proline hydroxylation of HIF-1alpha through binding to HIF-1alpha/PHD2. Proline 98-105 hypoxia inducible factor 1 subunit alpha Homo sapiens 123-133 24563687-0 2014 Proline-hydroxylated hypoxia-inducible factor 1alpha (HIF-1alpha) upregulation in human tumours. Proline 0-7 hypoxia inducible factor 1 subunit alpha Homo sapiens 21-52 24563687-0 2014 Proline-hydroxylated hypoxia-inducible factor 1alpha (HIF-1alpha) upregulation in human tumours. Proline 0-7 hypoxia inducible factor 1 subunit alpha Homo sapiens 54-64 24563687-4 2014 To this end we optimised antibodies against the proline-hydroxylated forms of HIF-1alpha for use in formalin fixed paraffin embedded (FFPE) immunohistochemistry to assess effects in tumour cells in vivo. Proline 48-55 hypoxia inducible factor 1 subunit alpha Homo sapiens 78-88 24563687-5 2014 We found that HIF-1alpha proline-hydroxylated at both VHL binding sites (Pro402 and Pro564), was present in hypoxic regions of a wide range of tumours, tumour xenografts and in moderately hypoxic cells in vitro. Proline 25-32 hypoxia inducible factor 1 subunit alpha Homo sapiens 14-24 24563687-8 2014 Our conclusions are that the degradation of proline-hydroxylated HIF-1alpha may be rate-limited in tumours and therefore provides new insights into mechanisms of HIF upregulation. Proline 44-51 hypoxia inducible factor 1 subunit alpha Homo sapiens 65-75 24563687-9 2014 Persistence of proline-hydroxylated HIF-1alpha in perinecrotic areas suggests there is adequate oxygen to support prolyl hydroxylase domain (PHD) activity and proline-hydroxylated HIF-1alpha may be the predominant form associated with the poorer prognosis that higher levels of HIF-1alpha confer. Proline 15-22 hypoxia inducible factor 1 subunit alpha Homo sapiens 36-46 24563687-9 2014 Persistence of proline-hydroxylated HIF-1alpha in perinecrotic areas suggests there is adequate oxygen to support prolyl hydroxylase domain (PHD) activity and proline-hydroxylated HIF-1alpha may be the predominant form associated with the poorer prognosis that higher levels of HIF-1alpha confer. Proline 159-166 hypoxia inducible factor 1 subunit alpha Homo sapiens 180-190 24563687-9 2014 Persistence of proline-hydroxylated HIF-1alpha in perinecrotic areas suggests there is adequate oxygen to support prolyl hydroxylase domain (PHD) activity and proline-hydroxylated HIF-1alpha may be the predominant form associated with the poorer prognosis that higher levels of HIF-1alpha confer. Proline 159-166 hypoxia inducible factor 1 subunit alpha Homo sapiens 180-190 23416007-2 2013 While HIF-1alpha in hypoxia translocates to the nucleus where it transcribes the target genes including vascular endothelial growth factor (VEGF) mRNA, HIF-1alpha is degraded under normoxia, which involves its proline hydroxylation and subsequent binding to the von Hippel-Lindau protein-Elongin B-Elogin C (VBC) complex. Proline 210-217 hypoxia inducible factor 1 subunit alpha Homo sapiens 6-16 23886708-0 2013 In silico investigation of PHD-3 specific HIF1-alpha proline 567 hydroxylation: a new player in the VHL/HIF-1alpha interaction pathway? Proline 53-60 hypoxia inducible factor 1 subunit alpha Homo sapiens 42-52 23886708-2 2013 This mechanism is mediated through hydroxylation of HIF-1alpha proline 564, although in vitro tests have previously shown an alternative hydroxylation at proline 567 by PHD-3. Proline 63-70 hypoxia inducible factor 1 subunit alpha Homo sapiens 52-62 23487784-7 2013 Moreover, expression of HIF-1alpha in cells that express PHD2 does not induce dedifferentiation but expression of HIF-1alpha containing mutations in the proline residues that are hydroxylated by PHD2 induces dedifferentiation. Proline 153-160 hypoxia inducible factor 1 subunit alpha Homo sapiens 114-124 24132642-1 2013 Hypoxia-inducible factor 1 (HIF-1) is regulated by the oxygen-dependent hydroxylation of proline residues by prolyl hydroxylases (PHDs). Proline 89-96 hypoxia inducible factor 1 subunit alpha Homo sapiens 0-26 24132642-1 2013 Hypoxia-inducible factor 1 (HIF-1) is regulated by the oxygen-dependent hydroxylation of proline residues by prolyl hydroxylases (PHDs). Proline 89-96 hypoxia inducible factor 1 subunit alpha Homo sapiens 28-33 23416007-2 2013 While HIF-1alpha in hypoxia translocates to the nucleus where it transcribes the target genes including vascular endothelial growth factor (VEGF) mRNA, HIF-1alpha is degraded under normoxia, which involves its proline hydroxylation and subsequent binding to the von Hippel-Lindau protein-Elongin B-Elogin C (VBC) complex. Proline 210-217 hypoxia inducible factor 1 subunit alpha Homo sapiens 152-162 20972335-4 2010 Oxygen-dependent changes in HIF-1alpha levels are regulated by proline hydroxylation and proteasomal degradation. Proline 63-70 hypoxia inducible factor 1 subunit alpha Homo sapiens 28-38 22181812-9 2012 A mutated HIF-1alpha protein, which has proline residues that were replaced with alanine and transfected into HEK293 cells, was not affected by the combination of LS081 and FeAC. Proline 40-47 hypoxia inducible factor 1 subunit alpha Homo sapiens 10-20 22286099-2 2012 In high O(2) tension (normoxia) the PHDs hydroxylate two conserved proline residues on HIF-1alpha, which leads to binding of the von Hippel-Lindau (VHL) tumour suppressor, the recognition component of a ubiquitin-ligase complex, initiating HIF-1alpha ubiquitylation and degradation. Proline 67-74 hypoxia inducible factor 1 subunit alpha Homo sapiens 87-97 22286099-2 2012 In high O(2) tension (normoxia) the PHDs hydroxylate two conserved proline residues on HIF-1alpha, which leads to binding of the von Hippel-Lindau (VHL) tumour suppressor, the recognition component of a ubiquitin-ligase complex, initiating HIF-1alpha ubiquitylation and degradation. Proline 67-74 hypoxia inducible factor 1 subunit alpha Homo sapiens 240-250 22134239-2 2011 High oxygen tension promotes proteosomal degradation of HIF-1alpha via a pathway that requires hydroxylation of prolines 402 and 564. Proline 112-120 hypoxia inducible factor 1 subunit alpha Homo sapiens 56-66 21335549-8 2011 Hydroxylation at the three sites in endogenous human HIF-1alpha proteins was suppressed by hypoxia in the order Pro(402) > Pro(564) > Asn(803). Proline 112-115 hypoxia inducible factor 1 subunit alpha Homo sapiens 53-63 21287578-3 2011 In normoxia, HIF-1alpha is destabilized by post-translational hydroxylation of Pro-564 and Pro-402 by a family of oxygen-sensitive dioxygenases. Proline 79-82 hypoxia inducible factor 1 subunit alpha Homo sapiens 13-23 21993963-2 2012 3.4.13.9] activity, proline or hydroxyproline, contribute to up-regulation of hypoxia-inducible factor-1alpha (HIF-1alpha). Proline 20-27 hypoxia inducible factor 1 subunit alpha Homo sapiens 78-109 21993963-2 2012 3.4.13.9] activity, proline or hydroxyproline, contribute to up-regulation of hypoxia-inducible factor-1alpha (HIF-1alpha). Proline 20-27 hypoxia inducible factor 1 subunit alpha Homo sapiens 111-121 21344271-2 2011 In the HIF1A P582S gene polymorphism (C1772T; rs 11549465 C/T), a single nucleotide transition from C T alters the codon sequence from the usual amino acid; proline (C-allele), to serine (T-allele). Proline 159-166 hypoxia inducible factor 1 subunit alpha Homo sapiens 7-12 21410436-7 2011 Using LC-MS/MS (liquid chromatography-tandem MS) detection, we show that all three PHD isoenzymes have a strong preference for hydroxylation of the CODDD proline residue over the NODDD proline residue and the preference is observed for both HIF1alpha and HIF2alpha protein substrates. Proline 154-161 hypoxia inducible factor 1 subunit alpha Homo sapiens 241-250 21785006-7 2011 Interaction with HIF-1alpha is facilitated by hydroxylation of PKM2 at proline-403 and -408 by PHD3. Proline 71-78 hypoxia inducible factor 1 subunit alpha Homo sapiens 17-27 20967267-7 2010 E-PE tissues had markedly diminished HIF-1alpha hydroxylation at proline residues 402 and 564 as assessed with monoclonal antibodies raised against hydroxylated HIF-1alpha P402 or P564, suggesting regulation by PHD2 and not PHD3. Proline 65-72 hypoxia inducible factor 1 subunit alpha Homo sapiens 37-47 20675386-2 2010 HIF-1alpha protein accumulates in hypoxia due to inhibition of prolyl hydroxylase enzymes, which under normoxic conditions use molecular oxygen to hydroxylate HIF-1alpha on two conserved proline residues (Pro(402) and Pro(564)), thus targeting the protein for 26 S proteasome-dependent degradation. Proline 187-194 hypoxia inducible factor 1 subunit alpha Homo sapiens 0-10 20675386-2 2010 HIF-1alpha protein accumulates in hypoxia due to inhibition of prolyl hydroxylase enzymes, which under normoxic conditions use molecular oxygen to hydroxylate HIF-1alpha on two conserved proline residues (Pro(402) and Pro(564)), thus targeting the protein for 26 S proteasome-dependent degradation. Proline 187-194 hypoxia inducible factor 1 subunit alpha Homo sapiens 159-169 20675386-2 2010 HIF-1alpha protein accumulates in hypoxia due to inhibition of prolyl hydroxylase enzymes, which under normoxic conditions use molecular oxygen to hydroxylate HIF-1alpha on two conserved proline residues (Pro(402) and Pro(564)), thus targeting the protein for 26 S proteasome-dependent degradation. Proline 205-208 hypoxia inducible factor 1 subunit alpha Homo sapiens 0-10 20675386-2 2010 HIF-1alpha protein accumulates in hypoxia due to inhibition of prolyl hydroxylase enzymes, which under normoxic conditions use molecular oxygen to hydroxylate HIF-1alpha on two conserved proline residues (Pro(402) and Pro(564)), thus targeting the protein for 26 S proteasome-dependent degradation. Proline 205-208 hypoxia inducible factor 1 subunit alpha Homo sapiens 159-169 20675386-2 2010 HIF-1alpha protein accumulates in hypoxia due to inhibition of prolyl hydroxylase enzymes, which under normoxic conditions use molecular oxygen to hydroxylate HIF-1alpha on two conserved proline residues (Pro(402) and Pro(564)), thus targeting the protein for 26 S proteasome-dependent degradation. Proline 218-221 hypoxia inducible factor 1 subunit alpha Homo sapiens 0-10 20675386-2 2010 HIF-1alpha protein accumulates in hypoxia due to inhibition of prolyl hydroxylase enzymes, which under normoxic conditions use molecular oxygen to hydroxylate HIF-1alpha on two conserved proline residues (Pro(402) and Pro(564)), thus targeting the protein for 26 S proteasome-dependent degradation. Proline 218-221 hypoxia inducible factor 1 subunit alpha Homo sapiens 159-169 20216986-10 2010 Thereby, Ruk/CIN85 interfered with the proline hydroxylation-dependent HIF-1alpha protein destabilisation. Proline 39-46 hypoxia inducible factor 1 subunit alpha Homo sapiens 71-81 20416277-2 2010 Oxygen- and 2-oxoglutarate (2-OG)-dependent, iron(II) containing HIF-specific prolyl-4-hydroxylases (PHDs) and factor inhibiting HIF-1alpha (FIH-1) catalyze the hydroxylation of the specific proline and asparagine residues of HIF-1alpha, thereby controlling the level of HIF-1alpha and ultimately the HIF response. Proline 191-198 hypoxia inducible factor 1 subunit alpha Homo sapiens 129-139 19958256-6 2010 Thereby quercetin interfered with the proline hydroxylation-dependent HIF-1alpha protein destabilization in the N-terminal HIF-1alpha transactivation domain. Proline 38-45 hypoxia inducible factor 1 subunit alpha Homo sapiens 70-80 19958256-6 2010 Thereby quercetin interfered with the proline hydroxylation-dependent HIF-1alpha protein destabilization in the N-terminal HIF-1alpha transactivation domain. Proline 38-45 hypoxia inducible factor 1 subunit alpha Homo sapiens 123-133 20461086-1 2010 Originally identified as the enzymes responsible for catalysing the oxidation of specific, conserved proline residues within hypoxia-inducible factor-1alpha (HIF-1alpha), the additional roles for the prolyl hydroxylase domain (PHD) proteins have remained elusive. Proline 101-108 hypoxia inducible factor 1 subunit alpha Homo sapiens 125-156 20461086-1 2010 Originally identified as the enzymes responsible for catalysing the oxidation of specific, conserved proline residues within hypoxia-inducible factor-1alpha (HIF-1alpha), the additional roles for the prolyl hydroxylase domain (PHD) proteins have remained elusive. Proline 101-108 hypoxia inducible factor 1 subunit alpha Homo sapiens 158-168 19603255-3 2009 An HIF-1alpha mutant, produced by substitution of alanine (Ala) for proline (Pro) at position 564 and asparagine (Asp) at position 803, can prevent HIF-1alpha hydroxylation and results in a highly active form of HIF-1alpha (HIF-1alpha-Ala564-Ala803). Proline 68-75 hypoxia inducible factor 1 subunit alpha Homo sapiens 3-13 19603255-3 2009 An HIF-1alpha mutant, produced by substitution of alanine (Ala) for proline (Pro) at position 564 and asparagine (Asp) at position 803, can prevent HIF-1alpha hydroxylation and results in a highly active form of HIF-1alpha (HIF-1alpha-Ala564-Ala803). Proline 77-80 hypoxia inducible factor 1 subunit alpha Homo sapiens 3-13 19603255-3 2009 An HIF-1alpha mutant, produced by substitution of alanine (Ala) for proline (Pro) at position 564 and asparagine (Asp) at position 803, can prevent HIF-1alpha hydroxylation and results in a highly active form of HIF-1alpha (HIF-1alpha-Ala564-Ala803). Proline 77-80 hypoxia inducible factor 1 subunit alpha Homo sapiens 148-158 19603255-3 2009 An HIF-1alpha mutant, produced by substitution of alanine (Ala) for proline (Pro) at position 564 and asparagine (Asp) at position 803, can prevent HIF-1alpha hydroxylation and results in a highly active form of HIF-1alpha (HIF-1alpha-Ala564-Ala803). Proline 77-80 hypoxia inducible factor 1 subunit alpha Homo sapiens 148-158 19603255-3 2009 An HIF-1alpha mutant, produced by substitution of alanine (Ala) for proline (Pro) at position 564 and asparagine (Asp) at position 803, can prevent HIF-1alpha hydroxylation and results in a highly active form of HIF-1alpha (HIF-1alpha-Ala564-Ala803). Proline 77-80 hypoxia inducible factor 1 subunit alpha Homo sapiens 148-158 18440561-3 2008 For therapeutic angiogenesis purposes, HIF-1 alpha stabilization was previously achieved by either deleting its oxygen-dependent degradation domains, or introducing two proline point mutations at residues P402 and P564. Proline 169-176 hypoxia inducible factor 1 subunit alpha Homo sapiens 39-50 19515556-1 2009 Hypoxia-inducible factor (HIF)-1alpha undergoes degradation under normoxia, which involves its proline hydroxylation and subsequent binding of proline-hydroxylated HIF-1alpha to the von Hippel-Lindau protein-Elongin B-Elongin C (VBC) complex. Proline 95-102 hypoxia inducible factor 1 subunit alpha Homo sapiens 0-37 19515556-1 2009 Hypoxia-inducible factor (HIF)-1alpha undergoes degradation under normoxia, which involves its proline hydroxylation and subsequent binding of proline-hydroxylated HIF-1alpha to the von Hippel-Lindau protein-Elongin B-Elongin C (VBC) complex. Proline 143-150 hypoxia inducible factor 1 subunit alpha Homo sapiens 0-37 19515556-1 2009 Hypoxia-inducible factor (HIF)-1alpha undergoes degradation under normoxia, which involves its proline hydroxylation and subsequent binding of proline-hydroxylated HIF-1alpha to the von Hippel-Lindau protein-Elongin B-Elongin C (VBC) complex. Proline 143-150 hypoxia inducible factor 1 subunit alpha Homo sapiens 164-174 19515556-2 2009 In this study, we designed and synthesized a series of peptides containing 556-575 residues of HIF-1alpha with modifications at the Pro-564 residue to inhibit the interaction between proline-hydroxylated HIF-1alpha and VBC. Proline 132-135 hypoxia inducible factor 1 subunit alpha Homo sapiens 95-105 19515556-2 2009 In this study, we designed and synthesized a series of peptides containing 556-575 residues of HIF-1alpha with modifications at the Pro-564 residue to inhibit the interaction between proline-hydroxylated HIF-1alpha and VBC. Proline 132-135 hypoxia inducible factor 1 subunit alpha Homo sapiens 204-214 19515556-2 2009 In this study, we designed and synthesized a series of peptides containing 556-575 residues of HIF-1alpha with modifications at the Pro-564 residue to inhibit the interaction between proline-hydroxylated HIF-1alpha and VBC. Proline 183-190 hypoxia inducible factor 1 subunit alpha Homo sapiens 95-105 19515556-2 2009 In this study, we designed and synthesized a series of peptides containing 556-575 residues of HIF-1alpha with modifications at the Pro-564 residue to inhibit the interaction between proline-hydroxylated HIF-1alpha and VBC. Proline 183-190 hypoxia inducible factor 1 subunit alpha Homo sapiens 204-214 19515556-5 2009 Considering that proline hydroxylation of HIF-1alpha is routinely targeted for modulating the HIF pathway, our approach of using inhibitors against the interactions between HIF-1alpha and VBC would provide an alternative way of upregulating HIF-1 activity. Proline 17-24 hypoxia inducible factor 1 subunit alpha Homo sapiens 42-52 19515556-5 2009 Considering that proline hydroxylation of HIF-1alpha is routinely targeted for modulating the HIF pathway, our approach of using inhibitors against the interactions between HIF-1alpha and VBC would provide an alternative way of upregulating HIF-1 activity. Proline 17-24 hypoxia inducible factor 1 subunit alpha Homo sapiens 173-183 19515556-5 2009 Considering that proline hydroxylation of HIF-1alpha is routinely targeted for modulating the HIF pathway, our approach of using inhibitors against the interactions between HIF-1alpha and VBC would provide an alternative way of upregulating HIF-1 activity. Proline 17-24 hypoxia inducible factor 1 subunit alpha Homo sapiens 42-47 19498081-1 2009 The prolyl-4-hydroxylase proteins regulate the hypoxia-inducible transcription factors (HIFs) by hydroxylation of proline residues targeting HIF-1alpha for proteasomal degradation. Proline 114-121 hypoxia inducible factor 1 subunit alpha Homo sapiens 141-151 18980686-4 2008 METHODS: Here we studied whether two single nucleotide sequence variants, c.1744 C>T that changes residue 582 of HIF-1alpha from proline to serine (P582S) and c.1762 G>A that changes residue 588 of HIF-1alpha from alanine to threonine (A588T) in the exon 12 of the HIF1A gene, are associated with pre-eclampsia. Proline 132-139 hypoxia inducible factor 1 subunit alpha Homo sapiens 116-126 19240858-5 2008 A relationship between HIF1A Ser allele and predominance of fast-twitch muscle fibers was shown (Pro/Ser 46.2 (13.8)%, Pro/Pro 31.4 (8.2)%; p=0.007). Proline 97-100 hypoxia inducible factor 1 subunit alpha Homo sapiens 23-28 19240858-5 2008 A relationship between HIF1A Ser allele and predominance of fast-twitch muscle fibers was shown (Pro/Ser 46.2 (13.8)%, Pro/Pro 31.4 (8.2)%; p=0.007). Proline 119-122 hypoxia inducible factor 1 subunit alpha Homo sapiens 23-28 19240858-5 2008 A relationship between HIF1A Ser allele and predominance of fast-twitch muscle fibers was shown (Pro/Ser 46.2 (13.8)%, Pro/Pro 31.4 (8.2)%; p=0.007). Proline 119-122 hypoxia inducible factor 1 subunit alpha Homo sapiens 23-28 18578010-3 2008 Hypoxia-responsive cis elements were used in tandem with a single proline-modified oxygen-dependent degradation (ODD) domain of hypoxia-inducible factor-1alpha to form a double oxygen-sensing vector system (DOSVS). Proline 66-73 hypoxia inducible factor 1 subunit alpha Homo sapiens 128-159 18503779-3 2008 However, under hypoxic conditions, the ubiquitination system for HIF-1 alpha is inhibited by inactivation of prolyl hydroxylase which is responsible for hydroxylation of proline in the oxygen-dependent degradation domain of HIF-1 alpha. Proline 170-177 hypoxia inducible factor 1 subunit alpha Homo sapiens 65-76 18503779-3 2008 However, under hypoxic conditions, the ubiquitination system for HIF-1 alpha is inhibited by inactivation of prolyl hydroxylase which is responsible for hydroxylation of proline in the oxygen-dependent degradation domain of HIF-1 alpha. Proline 170-177 hypoxia inducible factor 1 subunit alpha Homo sapiens 224-235 18694926-5 2008 We have performed a detailed analysis of a mutant form of HIF-1alpha, where both these proline residues have been mutated, and we have uncovered a novel degradation pathway, to which the HIF-1alpha mutant protein is not resistant. Proline 87-94 hypoxia inducible factor 1 subunit alpha Homo sapiens 58-68 18694926-5 2008 We have performed a detailed analysis of a mutant form of HIF-1alpha, where both these proline residues have been mutated, and we have uncovered a novel degradation pathway, to which the HIF-1alpha mutant protein is not resistant. Proline 87-94 hypoxia inducible factor 1 subunit alpha Homo sapiens 187-197 18694926-6 2008 Our results show that the HIF-1alpha double proline mutant undergoes ubiquitination and proteasome-dependent degradation, and retains the ability to be stabilized in response to hypoxia and CoCl(2) treatment. Proline 44-51 hypoxia inducible factor 1 subunit alpha Homo sapiens 26-36 18426857-7 2008 Instead, it blocked the interaction between VHL and the proline-hydroxylated HIF-1alpha, but only when the reducing agents Fe(II) and vitamin C were limiting. Proline 56-63 hypoxia inducible factor 1 subunit alpha Homo sapiens 77-87 17406354-4 2007 Accordingly, proline allele transiently transfected cell lines express lower levels of hypoxia pro-survival genes (HIF-1alpha, carbonic anhydrase IX, vascular endothelial growth factor, heme oxygenase-I, hepatocyte growth factor receptor, vascular endothelial growth factor receptor 2), compared to those transiently transfected with the arginine allele. Proline 13-20 hypoxia inducible factor 1 subunit alpha Homo sapiens 115-125 17942596-2 2008 Under normal oxygen conditions, HIF-1alpha, the active subunit of HIF-1, is hydroxylated on proline residues by specific HIF prolyl-hydroxylases, leading to ubiquitination and degradation by the proteasome. Proline 92-99 hypoxia inducible factor 1 subunit alpha Homo sapiens 32-42 17942596-2 2008 Under normal oxygen conditions, HIF-1alpha, the active subunit of HIF-1, is hydroxylated on proline residues by specific HIF prolyl-hydroxylases, leading to ubiquitination and degradation by the proteasome. Proline 92-99 hypoxia inducible factor 1 subunit alpha Homo sapiens 32-37 17412315-5 2007 Mechanistically, NO blocks PHD activity and attenuates proline hydroxylation of HIF-1alpha. Proline 55-62 hypoxia inducible factor 1 subunit alpha Homo sapiens 80-90 17551816-2 2007 O(2)-dependent hydroxylation of two proline residues in the HIF-1alpha subunit is necessary for the binding of the von Hippel-Lindau (VHL) protein, which is a component of a ubiquitin protein ligase that ubiquitinates HIF-1alpha, leading to its degradation by the proteasome. Proline 36-43 hypoxia inducible factor 1 subunit alpha Homo sapiens 60-70 17551816-2 2007 O(2)-dependent hydroxylation of two proline residues in the HIF-1alpha subunit is necessary for the binding of the von Hippel-Lindau (VHL) protein, which is a component of a ubiquitin protein ligase that ubiquitinates HIF-1alpha, leading to its degradation by the proteasome. Proline 36-43 hypoxia inducible factor 1 subunit alpha Homo sapiens 218-228 17172857-5 2006 At normoxia HIF-1alpha is hydroxylated at specific proline residues by a recently identified family of prolyl hydroxylases. Proline 51-58 hypoxia inducible factor 1 subunit alpha Homo sapiens 12-22 17189520-4 2007 Interaction with VHL requires hydroxylation of HIF-1alpha proline residues by prolyl hydroxylases (PHDs). Proline 58-65 hypoxia inducible factor 1 subunit alpha Homo sapiens 47-57 17002676-8 2006 Non-heme ferrous iron containing hydroxylases use dioxygen and 2-oxoglutarate to specifically target proline and an asparagine residue in HIF-1alpha. Proline 101-108 hypoxia inducible factor 1 subunit alpha Homo sapiens 138-148 16753841-0 2006 Peroxynitrite as an alternative donor of oxygen in HIF-1alpha proline hydroxylation under low oxygen availability. Proline 62-69 hypoxia inducible factor 1 subunit alpha Homo sapiens 51-61 16837101-2 2006 METHODS: Specific HIF-1alpha polymorphisms were assessed in a series of patients with NSCLC: (a) the C to T transition at nucleotide 1744 (position 2028 according to sequence with accession number , which gives rise to Pro/Ser variation at codon 582), (b) the G to A nucleotide substitution at point 1790 (position 2046 according to sequence with accession number , which gives rise to Ala/Thr variation at codon 588), and (c) the dinucleotide GT repeat polymorphism in intron 13. Proline 219-222 hypoxia inducible factor 1 subunit alpha Homo sapiens 18-28 16611863-4 2006 The degradation requires formation of a multiprotein complex (VHLCBC) and hydroxylation of HIF1A proline residues via members of the egg-laying-defective nine (EGLN) family. Proline 97-104 hypoxia inducible factor 1 subunit alpha Homo sapiens 91-96 16753841-4 2006 Here, we propose a hypothesis that peroxynitrite, formed in the cells upon exposure to NO under low oxygen availability, serves as an alternative donor of oxygen for activated PHDs so they can perform HIF-1alpha proline hydroxylation to de-accumulate the protein. Proline 212-219 hypoxia inducible factor 1 subunit alpha Homo sapiens 201-211 16182243-2 2005 This process requires hydroxylation of specific prolines in HIF-1alpha by HIF prolyl hydroxylase domain (PHD)-containing enzymes, leading to its specific interactions with von Hippel-Lindau protein-Elongin B-Elongin C (VBC). Proline 48-56 hypoxia inducible factor 1 subunit alpha Homo sapiens 60-70 16176182-5 2006 Drosophila PHD has a low substrate specificity and hydroxylates key proline residues in the ODD (oxygen-dependent degradation) domains of human HIF-1alpha and Similar, the Drosophila homologue of HIF-1alpha. Proline 68-75 hypoxia inducible factor 1 subunit alpha Homo sapiens 144-154 16155211-2 2005 An HIF-1alpha-specific prolyl-hydroxylase (PHD) catalyzes hydroxylation of the proline-564 and/or -402 residues of HIF-1alpha by an oxygen molecule. Proline 79-86 hypoxia inducible factor 1 subunit alpha Homo sapiens 3-13 16155211-2 2005 An HIF-1alpha-specific prolyl-hydroxylase (PHD) catalyzes hydroxylation of the proline-564 and/or -402 residues of HIF-1alpha by an oxygen molecule. Proline 79-86 hypoxia inducible factor 1 subunit alpha Homo sapiens 115-125 16139409-2 2006 In the presence of oxygen and iron, proline residues in two degradation domains are modified by HIF-1-prolyl hydroxylases (PHDs), resulting in ubiquitination and degradation of HIF-1alpha. Proline 36-43 hypoxia inducible factor 1 subunit alpha Homo sapiens 177-187 16139409-11 2006 The oxygen-dependent HIF-1alpha regulation requiring both proline hydroxylation and lysine acetylation may be more complicated than the iron-dependent regulation requiring only proline hydroxylation. Proline 58-65 hypoxia inducible factor 1 subunit alpha Homo sapiens 21-31 16139409-11 2006 The oxygen-dependent HIF-1alpha regulation requiring both proline hydroxylation and lysine acetylation may be more complicated than the iron-dependent regulation requiring only proline hydroxylation. Proline 177-184 hypoxia inducible factor 1 subunit alpha Homo sapiens 21-31 16100168-5 2005 DNA was genotyped for the presence of a single nucleotide (C to T) polymorphism that changes residue 582 of HIF-1alpha from proline to serine. Proline 124-131 hypoxia inducible factor 1 subunit alpha Homo sapiens 108-118 15485863-2 2004 We report here that the two leucines in the Leu-Glu-Met-Leu-Ala-Pro core motif of a 20-residue peptide corresponding to the sequence around Pro(564) in HIF-1alpha can be replaced by many residues with no or only a modest decrease in its substrate properties or in some cases even a slight increase. Proline 64-67 hypoxia inducible factor 1 subunit alpha Homo sapiens 152-162 16024780-2 2005 The alpha-subunit of HIF factor 1 (HIF-1) contains two highly conserved oxygen-dependent degradation domains (402 ODD and 564 ODD), each of which includes a proline that is hydroxylated in the presence of oxygen, allowing the von Hippel-Lindau (VHL) E3 ubiquitin ligase to interact and target HIF-1alpha to the proteasome for degradation. Proline 157-164 hypoxia inducible factor 1 subunit alpha Homo sapiens 35-40 16024780-3 2005 Mutation of either proline is sufficient to partially stabilize HIF-1alpha under conditions of normoxia, but the specific contributions of each hydroxylation event to the regulation of HIF-1alpha are unknown. Proline 19-26 hypoxia inducible factor 1 subunit alpha Homo sapiens 64-74 16024780-10 2005 These results indicate that hydroxylation of proline 402 is highly responsive to physiologic changes in oxygen and, therefore, plays a more important role in HIF-1alpha regulation under conditions of hypoxia than under conditions of normoxia. Proline 45-52 hypoxia inducible factor 1 subunit alpha Homo sapiens 158-168 16024780-11 2005 Together, these findings demonstrate that each hydroxylated proline of HIF-1alpha has a distinct activity in controlling HIF-1alpha stability in response to different levels of oxygenation. Proline 60-67 hypoxia inducible factor 1 subunit alpha Homo sapiens 71-81 16024780-11 2005 Together, these findings demonstrate that each hydroxylated proline of HIF-1alpha has a distinct activity in controlling HIF-1alpha stability in response to different levels of oxygenation. Proline 60-67 hypoxia inducible factor 1 subunit alpha Homo sapiens 121-131 15878343-2 2005 In normoxia, HIF-1alpha subunits are hydroxylated on specific proline residues; modifications that signal ubiquitination and degradation of HIF-1alpha by the proteasome. Proline 62-69 hypoxia inducible factor 1 subunit alpha Homo sapiens 13-23 15878343-2 2005 In normoxia, HIF-1alpha subunits are hydroxylated on specific proline residues; modifications that signal ubiquitination and degradation of HIF-1alpha by the proteasome. Proline 62-69 hypoxia inducible factor 1 subunit alpha Homo sapiens 140-150 15538748-6 2005 Increased expression of the P582S mutant induced by iron chelation, which blocks proline hydroxylation of wild-type HIF-1alpha, was markedly attenuated. Proline 81-88 hypoxia inducible factor 1 subunit alpha Homo sapiens 116-126 12186875-2 2002 Here, employing a novel hydroxylation-specific antibody, we directly show that proline 564 of HIF-1alpha and proline 531 of HIF-2alpha are hydroxylated under normoxia. Proline 79-86 hypoxia inducible factor 1 subunit alpha Homo sapiens 94-104 15271983-3 2004 It was shown recently that hydroxylation of prolines in the HIFalpha subunit of HIF-1 is required for its binding with the von Hippel-Lindau tumor suppressor protein and the subsequent proteasomal destruction. Proline 44-52 hypoxia inducible factor 1 subunit alpha Homo sapiens 80-85 14521712-2 2003 Under normoxic conditions, the alpha subunit of HIF is rapidly degraded in a manner dependent on hydroxylation of two conserved proline residues at positions 402 and 564 in HIF-1alpha in the oxygen-dependent degradation (ODD) domain. Proline 128-135 hypoxia inducible factor 1 subunit alpha Homo sapiens 173-183 12649278-2 2003 In normoxia, PHD hydroxylates a specific proline residue that directs the degradation of constitutively synthesized hypoxia-inducible factor-1alpha. Proline 41-48 hypoxia inducible factor 1 subunit alpha Homo sapiens 116-147 12649278-3 2003 During hypoxia, the cessation of hydroxylation of this proline results in less degradation and thus increases hypoxia-inducible factor-1alpha protein levels. Proline 55-62 hypoxia inducible factor 1 subunit alpha Homo sapiens 110-141 12586829-14 2003 We conclude that CsA destabilizes HIF-1alpha by promoting hydroxylation of Pro-564 in the ODD domain. Proline 75-78 hypoxia inducible factor 1 subunit alpha Homo sapiens 34-44 12670503-1 2003 Three HIF-alpha prolyl-4-hydroxylases (PHDs) (named PHD1, PHD2, and PHD3) effect the proteasome-mediated degradation of HIF by catalyzing the hydroxylation of key proline residues in the HIF-1 alpha subunit under normoxic conditions. Proline 163-170 hypoxia inducible factor 1 subunit alpha Homo sapiens 187-198 12181324-8 2002 Thus, these results provide evidence that the only obligatory residue for proline hydroxylation in HIF-1alpha is the hydroxylacceptor proline itself. Proline 74-81 hypoxia inducible factor 1 subunit alpha Homo sapiens 99-109 12181324-8 2002 Thus, these results provide evidence that the only obligatory residue for proline hydroxylation in HIF-1alpha is the hydroxylacceptor proline itself. Proline 134-141 hypoxia inducible factor 1 subunit alpha Homo sapiens 99-109 15350301-4 2004 These polymorphisms are found within the oxygen-dependent degradation domain of the HIF-1alpha protein and may be important in the oxygen regulation of the protein via hydroxylation of the proline residue at position 564 (P564) by HIF-alpha prolyl hydroxylase (HIF-PH). Proline 189-196 hypoxia inducible factor 1 subunit alpha Homo sapiens 84-94 15104534-2 2004 In normoxia, HIF-1alpha is destabilized by post-translational hydroxylation of Pro-564 and Pro-402 by a family of oxygen-sensitive dioxygenases. Proline 79-82 hypoxia inducible factor 1 subunit alpha Homo sapiens 13-23 14984367-4 2004 These enzymes are oxygen-, iron- and 2-oxoglutarate-dependent dioxygenases that hydroxylate key proline and asparagine residues in HIFalpha subunits. Proline 96-103 hypoxia inducible factor 1 subunit alpha Homo sapiens 131-139 15084514-5 2004 Recently, we demonstrated that Leu-574 of human HIF-1alpha--10 residues downstream of Pro-564--is essential for VHL recognition. Proline 86-89 hypoxia inducible factor 1 subunit alpha Homo sapiens 48-58 15084514-7 2004 An antibody specific for hydroxylated Pro-564 has been used to determine the hydroxylation status; mutation or deletion of Leu-574 results in a significant decrease in the ratio of the hydroxylated HIF-1alpha to the total amount. Proline 38-41 hypoxia inducible factor 1 subunit alpha Homo sapiens 198-208 12873125-2 2003 Recent studies demonstrated that PR39, a natural proline- and arginine-rich antibacterial peptide, stimulates angiogenesis and inhibits inflammatory responses by specifically blocking degradation of IkappaBalpha and HIF-1alpha by the proteasome. Proline 49-56 hypoxia inducible factor 1 subunit alpha Homo sapiens 216-226 12538644-3 2003 This process is dependent on the hydroxylation of conserved proline residues on the alpha subunits of HIF-1/2 in the presence of oxygen. Proline 60-67 hypoxia inducible factor 1 subunit alpha Homo sapiens 102-109 12393546-2 2003 The tumor suppressor von Hippel-Lindau (VHL) participates in the hypoxia-sensing pathway, as it binds to the proline-hydroxylated form of the hypoxia-inducible factor 1alpha (HIF-1alpha) and mediates its ubiquitination and proteosomal degradation. Proline 109-116 hypoxia inducible factor 1 subunit alpha Homo sapiens 142-173 12393546-2 2003 The tumor suppressor von Hippel-Lindau (VHL) participates in the hypoxia-sensing pathway, as it binds to the proline-hydroxylated form of the hypoxia-inducible factor 1alpha (HIF-1alpha) and mediates its ubiquitination and proteosomal degradation. Proline 109-116 hypoxia inducible factor 1 subunit alpha Homo sapiens 175-185 12205091-4 2002 In particular, the von Hippel-Lindau (VHL) protein complex, an E3 ubiquitin ligase, binds to the ODD upon hydroxylation of HIF-1alpha Pro-564. Proline 134-137 hypoxia inducible factor 1 subunit alpha Homo sapiens 123-133 12186875-3 2002 Importantly, HIF-1alpha Pro-564 and HIF-2alpha Pro-531 hydroxylation is diminished with the treatment of hypoxia, cobalt chloride, desferrioxamine, or dimethyloxalyglycine, regardless of the E3 ubiquitin ligase activity of the von Hippel-Lindau (VHL) tumor suppressor gene. Proline 24-27 hypoxia inducible factor 1 subunit alpha Homo sapiens 13-23 12186875-3 2002 Importantly, HIF-1alpha Pro-564 and HIF-2alpha Pro-531 hydroxylation is diminished with the treatment of hypoxia, cobalt chloride, desferrioxamine, or dimethyloxalyglycine, regardless of the E3 ubiquitin ligase activity of the von Hippel-Lindau (VHL) tumor suppressor gene. Proline 47-50 hypoxia inducible factor 1 subunit alpha Homo sapiens 13-23 12186875-4 2002 Furthermore, in VHL-deficient cells, HIF-1alpha Pro-564 and HIF-2alpha Pro-531 had detectable amounts of hydroxylation following transition to hypoxia, indicating that the post-translational modification is not reversible. Proline 48-51 hypoxia inducible factor 1 subunit alpha Homo sapiens 37-47 11292861-4 2001 Here we show that the interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by an enzyme we have termed HIF-alpha prolyl-hydroxylase (HIF-PH). Proline 141-148 hypoxia inducible factor 1 subunit alpha Homo sapiens 82-92 11504942-0 2001 HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proline 61-68 hypoxia inducible factor 1 subunit alpha Homo sapiens 0-10 12124396-3 2002 One sequence was adjacent to and the other coincided with the two proline residues of the oxygen-dependent degradation domain (P402 and P564) that act as switches for the oxygen-dependent regulation of HIF-1alpha. Proline 66-73 hypoxia inducible factor 1 subunit alpha Homo sapiens 202-212 12124396-7 2002 The binding data support the proposal that p53 provides a route for the degradation in hypoxic tumor cells of HIF-1alpha that is not hydroxylated at the two proline residues. Proline 157-164 hypoxia inducible factor 1 subunit alpha Homo sapiens 110-120 12195866-6 2002 The underlying oxygen sensor is provided by a family of enzymes which oxidize specific proline residues in HIF alpha subunits. Proline 87-94 hypoxia inducible factor 1 subunit alpha Homo sapiens 107-116 11292861-4 2001 Here we show that the interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by an enzyme we have termed HIF-alpha prolyl-hydroxylase (HIF-PH). Proline 141-148 hypoxia inducible factor 1 subunit alpha Homo sapiens 158-168