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Literature summary for 1.14.11.29 extracted from

  • Li, J.; Yuan, W.; Jiang, S.; Ye, W.; Yang, H.; Shapiro, I.M.; Risbud, M.V.
    Prolyl-4-hydroxylase domain protein 2 controls NF-kappaB/p65 transactivation and enhances the catabolic effects of inflammatory cytokines on cells of the nucleus pulposus (2015), J. Biol. Chem., 290, 7195-7207 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.14.11.29

Application

Application Comment Organism
medicine during disc degeneration PHD2 may offer a therapeutic target to mitigate the deleterious actions of TNF-alpha, a key proinflammatory cytokine Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene EGLN1, recombinant expression in HEK 293T cells from vector pRL-TK containing Renilla reniformis luciferase gene, real-time RT-PCR enzyme expression analysis Homo sapiens
gene EGLN1, recombinant expression in HEK 293T cells from vector pRL-TK containing Renilla reniformis luciferase gene, real-time RT-PCR enzyme expression analysis Rattus norvegicus

Protein Variants

Protein Variants Comment Organism
additional information PDH2 knockout in NP cells lentiviral expression of shPHD2, phenotype, overview. TNF-alpha-dependent induction in expression of PHD3, SDC4, MMP13, and ADAMTS5, catabolic marker genes that are hallmark of disc degeneration, is significantly reduced in PHD2 silenced cells. Silencing of PHD2 significantly restores the TNF-alpha-mediated reduction in aggrecan sand collagen II Rattus norvegicus

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
-
 hypoxia-inducible factor-alpha-trans-4-hydroxy-L-proline + succinate + CO2
-
 ?
hypoxia-inducible factor-alpha-L-proline + 2-oxoglutarate + O2 Rattus norvegicus
-
 hypoxia-inducible factor-alpha-trans-4-hydroxy-L-proline + succinate + CO2
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9GZT9
-
-
Rattus norvegicus P59722
-
-

Source Tissue

Source Tissue Comment Organism Textmining
intervertebral disc
-
 Homo sapiens
-
intervertebral disc
-
 Rattus norvegicus
-
nucleus pulposus NP cell Homo sapiens
-
nucleus pulposus NP cell Rattus norvegicus
-

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
-
 ?
hypoxia-inducible factor-alpha-L-proline + 2-oxoglutarate + O2
-
 Rattus norvegicus hypoxia-inducible factor-alpha-trans-4-hydroxy-L-proline + succinate + CO2
-
 ?

Synonyms

Synonyms Comment Organism
PHD2
-
 Homo sapiens
PHD2
-
 Rattus norvegicus
prolyl-4-hydroxylase 2
-
 Homo sapiens
prolyl-4-hydroxylase 2
-
 Rattus norvegicus

General Information

General Information Comment Organism
metabolism PHD isoforms have a differential contribution in controlling hypoxia-inducible factor (HIF)-alpha degradation and activity Homo sapiens
metabolism PHD isoforms have a differential contribution in controlling hypoxia-inducible factor (HIF)-alpha degradation and activity Rattus norvegicus
physiological function PHD2 controls the expression of many of the pro-catabolic and inflammatory genes that are known to be involved with the degenerative cascade and matrix breakdown. Prolyl-4-hydroxylase domain protein 2 controls NF-kappaB/p65 transactivation and enhances the catabolic effects of inflammatory cytokines on cells of the nucleus pulposus, regulatory mechanism of PHD2 function and expression under inflammatory conditions in the nucleus pulposus, overview. PHD2 controls TNF-alpha effects by positively regulating NF-kappaB signaling, whereas NF-kappaB mediates cytokine-dependent PHD2 expression. PHD2 and NF-kappaB form a functional circuit that promotes the catabolic effects of TNF-alpha in the intervertebral disc. PHD2 is a potent regulator of the catabolic activities of TNF-alpha, silencing of PHD2 significantly decreases TNF-alpha-induced expression of catabolic markers including SDC4, MMP-3, MMP-13, and ADAMTS5, as well as several inflammatory cytokines and chemokines, while partially restoring aggrecan and collagen II expression Homo sapiens
physiological function PHD2 controls the expression of many of the pro-catabolic and inflammatory genes that are known to be involved with the degenerative cascade and matrix breakdown. Prolyl-4-hydroxylase domain protein 2 controls NF-kappaB/p65 transactivation and enhances the catabolic effects of inflammatory cytokines on cells of the nucleus pulposus, regulatory mechanism of PHD2 function and expression under inflammatory conditions in the nucleus pulposus, overview. PHD2 controls TNF-alpha effects by positively regulating NF-kappaB signaling, whereas NF-kappaB mediates cytokine-dependent PHD2 expression. PHD2 and NF-kappaB form a functional circuit that promotes the catabolic effects of TNF-alpha in the intervertebral disc. PHD2 is a potent regulator of the catabolic activities of TNF-alpha, silencing of PHD2 significantly decreases TNF-alpha-induced expression of catabolic markers including SDC4, MMP-3, MMP-13, and ADAMTS5, as well as several inflammatory cytokines and chemokines, while partially restoring aggrecan and collagen II expression Rattus norvegicus