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Literature summary for 1.14.11.2 extracted from

  • Xiong, G.; Stewart, R.L.; Chen, J.; Gao, T.; Scott, T.L.; Samayoa, L.M.; OConnor, K.; Lane, A.N.; Xu, R.
    Collagen prolyl 4-hydroxylase 1 is essential for HIF-1alpha stabilization and TNBC chemoresistance (2018), Nat. Commun., 9, 4456 .
    View publication on PubMedView publication on EuropePMC
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Natural Substrates/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Homo sapiens P13674 P4H alpha 1 subunit
-

Substrates and Products (Substrate)

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

Synonyms

Synonyms Comment Organism
collagen prolyl 4-hydroxylase 1
-
 Homo sapiens
P4ha1 P4H alpha 1 subunit Homo sapiens

Expression

Organism Comment Expression
Homo sapiens P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer up

General Information

General Information Comment Organism
drug target targeting collagen P4H is a promising strategy to inhibit tumor progression and sensitize triple-negative breast cancer (TNBC) to chemotherapeutic agents. Inhibition of the enzyme (P4HA1) sensitizes triple-negative breast cancer (TNBC) to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived models. It is shown that increased P4HA1 expression correlates with short relapse-free survival in TNBC patients who received chemotherapy Homo sapiens
physiological function collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. 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. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. The enzyme is essential for HIF-1alpha stabilization and triple-negative breast cancer (TNBC)chemoresistance Homo sapiens