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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2002-8-7
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pubmed:abstractText |
There is evidence that hypoxia-inducible factor-1alpha (HIF-1alpha) interacts with the tumor suppressor p53. To characterize the putative interaction, we mapped the binding of the core domain of p53 (p53c) to an array of immobilized HIF-1alpha-derived peptides and found two peptide-sequence motifs that bound to p53c with micromolar affinity in solution. One sequence was adjacent to and the other coincided with the two proline residues of the oxygen-dependent degradation domain (P402 and P564) that act as switches for the oxygen-dependent regulation of HIF-1alpha. The binding affinity was independent of the hydroxylation state of P564. We found from NMR spectroscopy that these sequence motifs bind to the DNA-binding site of p53c. Because the two sequences are homologous and separated by 120 residues, and one is in a largely unstructured transactivation domain, we speculate that each sequence motif in HIF-1alpha binds to a different subunit of the p53 tetramer, leading to very tight binding. The binding data support the proposal that p53 provides a route for the degradation in hypoxic tumor cells of HIF-1alpha that is not hydroxylated at the two proline residues.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-10411893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-10549356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-10640274,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-10950862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11158315,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11237523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11292861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11292862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11566883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11593383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11595184,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11598268,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11782540,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11839490,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11865061,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-11877378,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-1537400,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-1662805,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-7539918,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-7929265,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-8023157,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-8065358,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-8875926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-9111021,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-9130695,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-9405613,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-9537326,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-9575138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12124396-9653127
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
99
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10305-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:12124396-Amino Acid Motifs,
pubmed-meshheading:12124396-Amino Acid Sequence,
pubmed-meshheading:12124396-Binding Sites,
pubmed-meshheading:12124396-DNA,
pubmed-meshheading:12124396-Humans,
pubmed-meshheading:12124396-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:12124396-Molecular Sequence Data,
pubmed-meshheading:12124396-Peptides,
pubmed-meshheading:12124396-Solutions,
pubmed-meshheading:12124396-Transcription Factors,
pubmed-meshheading:12124396-Tumor Suppressor Protein p53
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pubmed:year |
2002
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pubmed:articleTitle |
Two sequence motifs from HIF-1alpha bind to the DNA-binding site of p53.
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pubmed:affiliation |
Cambridge Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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