| http://purl.uniprot.org/citations/21335549 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21335549 | http://www.w3.org/2000/01/rdf-schema#comment | "Hypoxia inducible factor (HIF) is regulated by dual pathways involving oxygen-dependent prolyl and asparaginyl hydroxylation of its α-subunits. Prolyl hydroxylation at two sites within a central degradation domain promotes association of HIF-α with the von Hippel-Lindau ubiquitin E3 ligase and destruction by the ubiquitin-proteasome pathways. Asparaginyl hydroxylation blocks the recruitment of p300/CBP co-activators to a C-terminal activation domain in HIF-α. These hydroxylations are catalyzed by members of the Fe(II) and 2-oxoglutarate (2-OG) oxygenase family. Activity of the enzymes is suppressed by hypoxia, increasing both the abundance and activity of the HIF transcriptional complex. We have used hydroxy residue-specific antibodies to compare and contrast the regulation of each site of prolyl hydroxylation (Pro(402), Pro(564)) with that of asparaginyl hydroxylation (Asn(803)) in human HIF-1α. Our findings reveal striking differences in the sensitivity of these hydroxylations to hypoxia and to different inhibitor types of 2-OG oxygenases. Hydroxylation at the three sites in endogenous human HIF-1α proteins was suppressed by hypoxia in the order Pro(402) > Pro(564) > Asn(803). In contrast to some predictions from in vitro studies, prolyl hydroxylation was substantially more sensitive than asparaginyl hydroxylation to inhibition by iron chelators and transition metal ions; studies of a range of different small molecule 2-OG analogues demonstrated the feasibility of selectively inhibiting either prolyl or asparaginyl hydroxylation within cells."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m110.211110"xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/author | "Schofield C.J."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/author | "Kramer H.B."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/author | "Lee M.K."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/author | "Edelmann M.J."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/author | "Kessler B.M."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/author | "Ratcliffe P.J."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/author | "Eriksson T."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/author | "Pugh C.W."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/author | "Tian Y.M."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/author | "Willam C."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/author | "Yeoh K.K."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/pages | "13041-13051"xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/title | "Differential sensitivity of hypoxia inducible factor hydroxylation sites to hypoxia and hydroxylase inhibitors."xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://purl.uniprot.org/core/volume | "286"xsd:string |
| http://purl.uniprot.org/citations/21335549 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21335549 |
| http://purl.uniprot.org/citations/21335549 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21335549 |
| http://purl.uniprot.org/uniprot/#_A6NIX2-mappedCitation-21335549 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21335549 |
| http://purl.uniprot.org/uniprot/#_Q15369-mappedCitation-21335549 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21335549 |
| http://purl.uniprot.org/uniprot/#_Q15370-mappedCitation-21335549 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21335549 |
| http://purl.uniprot.org/uniprot/#_Q13617-mappedCitation-21335549 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21335549 |