@article{Amelio2015TAp73-57078,
  year={2015},
  doi={10.1073/pnas.1410609111},
  title={TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation},
  number={1},
  volume={112},
  issn={0027-8424},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  pages={226--231},
  author={Amelio, Ivano and Inoue, Satoshi and Markert, Elke K. and Levine, Arnold J. and Knight, Richard A. and Mak, Tak W. and Melino, Gerry}
}

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    <dc:contributor>Markert, Elke K.</dc:contributor>
    <dc:creator>Inoue, Satoshi</dc:creator>
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    <dc:contributor>Mak, Tak W.</dc:contributor>
    <dc:creator>Knight, Richard A.</dc:creator>
    <dc:contributor>Melino, Gerry</dc:contributor>
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    <dc:creator>Levine, Arnold J.</dc:creator>
    <dc:contributor>Levine, Arnold J.</dc:contributor>
    <dc:language>eng</dc:language>
    <dc:creator>Amelio, Ivano</dc:creator>
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    <dc:contributor>Amelio, Ivano</dc:contributor>
    <dc:contributor>Knight, Richard A.</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-03-30T09:08:00Z</dc:date>
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    <dcterms:title>TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation</dcterms:title>
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    <dc:contributor>Inoue, Satoshi</dc:contributor>
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    <dc:creator>Melino, Gerry</dc:creator>
    <dcterms:abstract xml:lang="eng">Tumor hypoxia and hypoxia-inducible factor 1 (HIF-1) activation are associated with cancer progression. Here, we demonstrate that the transcription factor TAp73 opposes HIF-1 activity through a nontranscriptional mechanism, thus affecting tumor angiogenesis. TAp73-deficient mice have an increased incidence of spontaneous and chemically induced tumors that also display enhanced vascularization. Mechanistically, TAp73 interacts with the regulatory subunit (α) of HIF-1 and recruits mouse double minute 2 homolog into the protein complex, thus promoting HIF-1α polyubiquitination and consequent proteasomal degradation in an oxygen-independent manner. In human lung cancer datasets, TAp73 strongly predicts good patient prognosis, and its expression is associated with low HIF-1 activation and angiogenesis. Our findings, supported by in vivo and clinical evidence, demonstrate a mechanism for oxygen-independent HIF-1 regulation, which has important implications for individualizing therapies in patients with cancer.</dcterms:abstract>
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