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Literature summary for 1.14.11.29 extracted from

  • Sun, W.; Jelkmann, W.; Depping, R.
    Prolyl-4-hydroxylase 2 enhances hypoxia-induced glioblastoma cell death by regulating the gene expression of hypoxia-inducible factor-alpha (2014), Cell Death Dis., 5, e1322 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.14.11.29

Application

Application Comment Organism
pharmacology modulation of PHD2 activity might be considered as a new way to inhibit glioblastoma progression Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene EGLN1 Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information siRNA against PHD2 causes sufficient PHD2 knockdown in glioblastoma cell lines U-87MG, U-138MG, and U-343MG Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
hypoxia-inducible factor-alpha-L-proline + 2-oxoglutarate + O2 Homo sapiens
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 hypoxia-inducible factor-alpha-trans-4-hydroxy-L-proline + succinate + CO2
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 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9GZT9
-
-

Source Tissue

Source Tissue Comment Organism Textmining
glioblastoma cell
-
 Homo sapiens
-
U-138MG cell
-
 Homo sapiens
-
U-343MG cell
-
 Homo sapiens
-
U-87MG cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
hypoxia-inducible factor-alpha-L-proline + 2-oxoglutarate + O2
-
 Homo sapiens hypoxia-inducible factor-alpha-trans-4-hydroxy-L-proline + succinate + CO2
-
 ?

Synonyms

Synonyms Comment Organism
EGLN1
-
 Homo sapiens
PHD2
-
 Homo sapiens
prolyl-4-hydroxylase 2
-
 Homo sapiens

General Information

General Information Comment Organism
malfunction the gene expression of p50 is reduced in the PHD2 knockdown cells, while the protein amount and the subcellular distribution of p65 are not changed in the PHD2 knockdown cells. The transactivation activity of NFkappaB is consequently decreased in the PHD2 knockdown cells. The expression levels of HIF target genes GLUT1 and VEGF-A is significantly upregulated in the PHD2 knockdown cells. The gene expression of BNIP3 is decreased. The influence of PHD2 knockdown on the gene expression of HIF-1alpha, HIF-2alpha, and p50 is not caused by off-target effect Homo sapiens
physiological function oxygen deprivation (hypoxia) is a common feature of solid tumors in advanced stages. The primary cellular transcriptional responses to hypoxia are mainly mediated by the transcription factor hypoxia-inducible factor (HIF). HIF consists of an oxygen-labile alpha-subunit (HIF-1alpha, HIF-2alpha) and a stable beta-subunit (ARNT). Prolyl-4-hydroxylase 2 (PHD2) is an important mediator of the oxygen-dependent degradation of HIF-alpha subunits. Prolyl-4-hydroxylase 2 enhances hypoxia-induced glioblastoma cell death by regulating the gene expression of hypoxia-inducible factor-alpha. In the glioblastoma cells, PHD2 maintains the gene expression of HIF-1alpha in dependence of nuclear factor kappaB and suppresses the gene expression of HIF-2alpha through HIF-1alpha. The PHD2-mediated degradation of HIF-1alpha and HIF-2alpha seems less important. PHD2 maintains the gene expression of the NFkappaB subunit p50 in glioblastoma cells. PHD2 enhances hypoxia-induced glioblastoma cell death by modulating the expression of the HIF target genes glucose transporter 1, vascular endothelial growth factor-A and Bcl-2 binding protein 3. PHD2 inhibits the adaptation of glioblastoma cells to hypoxia by regulating the HIF-alpha subunits in a non-canonical way. But exogenous PHD2 has no impact on the gene expression of HIF-1alpha and HIF-2alpha in glioblastoma cells Homo sapiens