| http://purl.uniprot.org/citations/26740011 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26740011 | http://www.w3.org/2000/01/rdf-schema#comment | "Prolyl hydroxylase domain protein 2 (PHD2) belongs to an evolutionarily conserved superfamily of 2-oxoglutarate and Fe(II)-dependent dioxygenases that mediates homeostatic responses to oxygen deprivation by mediating hypoxia-inducible factor-1α (HIF-1α) hydroxylation and degradation. Although oxidative stress contributes to the inactivation of PHD2, the precise molecular mechanism of PHD2 inactivation independent of the levels of co-factors is not understood. Here, we identified disulfide bond-mediated PHD2 homo-dimer formation in response to oxidative stress caused by oxidizing agents and oncogenic H-ras(V12) signalling. Cysteine residues in the double-stranded β-helix fold that constitutes the catalytic site of PHD isoforms appeared responsible for the oxidative dimerization. Furthermore, we demonstrated that disulfide bond-mediated PHD2 dimerization is associated with the stabilization and activation of HIF-1α under oxidative stress. Oncogenic H-ras(V12) signalling facilitates the accumulation of HIF-1α in the nucleus and promotes aerobic glycolysis and lactate production. Moreover, oncogenic H-ras(V12) does not trigger aerobic glycolysis in antioxidant-treated or PHD2 knocked-down cells, suggesting the participation of the ROS-mediated PHD2 inactivation in the oncogenic H-ras(V12)-mediated metabolic reprogramming. We provide here a better understanding of the mechanism by which disulfide bond-mediated PHD2 dimerization and inactivation result in the activation of HIF-1α and aerobic glycolysis in response to oxidative stress."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.org/dc/terms/identifier | "doi:10.1038/srep18928"xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Kim Y.J."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Lee G."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Puigserver P."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Choi J.W."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Lee Y.M."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Park J.W."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Lim J.H."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Won H.S."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Choi D.K."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Jang J.H."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Lim B.O."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/author | "Oh T.I."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/name | "Sci Rep"xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/pages | "18928"xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/title | "Oxidative Dimerization of PHD2 is Responsible for its Inactivation and Contributes to Metabolic Reprogramming via HIF-1alpha Activation."xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://purl.uniprot.org/core/volume | "6"xsd:string |
| http://purl.uniprot.org/citations/26740011 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26740011 |
| http://purl.uniprot.org/citations/26740011 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26740011 |
| http://purl.uniprot.org/uniprot/#_D0VY79-mappedCitation-26740011 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26740011 |
| http://purl.uniprot.org/uniprot/#_B2R617-mappedCitation-26740011 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26740011 |
| http://purl.uniprot.org/uniprot/#_A6XP74-mappedCitation-26740011 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26740011 |