Source:http://linkedlifedata.com/resource/pubmed/id/16223732
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
51
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pubmed:dateCreated |
2005-12-19
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pubmed:abstractText |
Continuous hydroxylation of the HIF-1 transcription factor alpha subunit by oxygen and 2-oxoglutarate-dependent dioxygenases promotes decay of this protein and thus prevents the transcriptional activation of many genes involved in energy metabolism, angiogenesis, cell survival, and matrix modification. Hypoxia blocks HIF-1alpha hydroxylation and thus activates HIF-1alpha-mediated gene expression. Several nonhypoxic stimuli can also activate HIF-1, although the mechanisms involved are not well known. Here we show that the glucose metabolites pyruvate and oxaloacetate inactivate HIF-1alpha decay in a manner selectively reversible by ascorbate, cysteine, histidine, and ferrous iron but not by 2-oxoglutarate or oxygen. Pyruvate and oxaloacetate bind to the 2-oxoglutarate site of HIF-1alpha prolyl hydroxylases, but their effects on HIF-1 are not mimicked by other Krebs cycle intermediates, including succinate and fumarate. We show that inactivation of HIF-1 hydroxylation by glucose-derived 2-oxoacids underlies the prominent basal HIF-1 activity commonly seen in many highly glycolytic cancer cells. Since HIF-1 itself promotes glycolytic metabolism, enhancement of HIF-1 by glucose metabolites may constitute a novel feed-forward signaling mechanism involved in malignant progression.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ascorbic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Histidine,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Oxaloacetate,
http://linkedlifedata.com/resource/pubmed/chemical/Procollagen-Proline Dioxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Pyruvic Acid
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
280
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
41928-39
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16223732-Ascorbic Acid,
pubmed-meshheading:16223732-Base Sequence,
pubmed-meshheading:16223732-Cell Line,
pubmed-meshheading:16223732-Cysteine,
pubmed-meshheading:16223732-DNA Primers,
pubmed-meshheading:16223732-Glutathione,
pubmed-meshheading:16223732-Glycolysis,
pubmed-meshheading:16223732-Histidine,
pubmed-meshheading:16223732-Humans,
pubmed-meshheading:16223732-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:16223732-Oxaloacetate,
pubmed-meshheading:16223732-Procollagen-Proline Dioxygenase,
pubmed-meshheading:16223732-Pyruvic Acid
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pubmed:year |
2005
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pubmed:articleTitle |
Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1.
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pubmed:affiliation |
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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