Abstract
Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that plays a crucial role in mediating oxygen response in the cell. Using biophysical techniques, we characterized two fragments of the HIF-1alpha subunit, one the full-length ODD domain (residues 403-603) and the second comprising the N-TAD (N-transactivation domain) and inhibitory domain (residues 530-698). Both were unstructured in solution under physiological conditions and so belong to the family of natively unfolded proteins. The HIF-1alpha ODD domain binds weakly to the isolated p53 core domain but tightly to full-length p53 to give a complex of one HIF-1alpha ODD domain with a p53 dimer. By being unstructured, the HIF-1alpha ODD domain can thread both its binding sites through the p53 multimer and bind tightly by the "chelate effect." These results support the idea that hypoxic p53-mediated apoptosis does involve the direct binding of HIF-1alpha to p53.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Base Sequence
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Binding Sites
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Circular Dichroism
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DNA / genetics
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Humans
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Hypoxia / metabolism
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Hypoxia / pathology
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Hypoxia-Inducible Factor 1
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Hypoxia-Inducible Factor 1, alpha Subunit
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In Vitro Techniques
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Kinetics
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Multiprotein Complexes
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Nuclear Proteins / chemistry*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Osmolar Concentration
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Protein Binding
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Protein Folding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Transcription Factors / chemistry*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Suppressor Protein p53 / chemistry
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
Substances
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DNA-Binding Proteins
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HIF1A protein, human
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Hypoxia-Inducible Factor 1
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Hypoxia-Inducible Factor 1, alpha Subunit
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Multiprotein Complexes
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Nuclear Proteins
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Peptide Fragments
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Recombinant Proteins
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Transcription Factors
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Tumor Suppressor Protein p53
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DNA