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TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation

TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation

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AMELIO, Ivano, Satoshi INOUE, Elke K. MARKERT, Arnold J. LEVINE, Richard A. KNIGHT, Tak W. MAK, Gerry MELINO, 2015. TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation. In: Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. 112(1), pp. 226-231. ISSN 0027-8424. eISSN 1091-6490. Available under: doi: 10.1073/pnas.1410609111

@article{Amelio2015TAp73-57078, title={TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation}, year={2015}, doi={10.1073/pnas.1410609111}, 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} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/57078"> <dc:contributor>Levine, Arnold J.</dc:contributor> <dc:creator>Mak, Tak W.</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:language>eng</dc:language> <dcterms:title>TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation</dcterms:title> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Inoue, Satoshi</dc:contributor> <dc:creator>Knight, Richard A.</dc:creator> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-03-30T09:08:00Z</dc:date> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:contributor>Amelio, Ivano</dc:contributor> <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:creator>Levine, Arnold J.</dc:creator> <dc:rights>terms-of-use</dc:rights> <dc:contributor>Melino, Gerry</dc:contributor> <dc:contributor>Markert, Elke K.</dc:contributor> <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> <dc:creator>Inoue, Satoshi</dc:creator> <dc:creator>Melino, Gerry</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-03-30T09:08:00Z</dcterms:available> <dcterms:issued>2015</dcterms:issued> <dc:contributor>Mak, Tak W.</dc:contributor> <dc:creator>Amelio, Ivano</dc:creator> <dc:contributor>Knight, Richard A.</dc:contributor> <dc:creator>Markert, Elke K.</dc:creator> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57078/1/Amelio_2-14peddrdr01sf4.pdf"/> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/57078"/> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57078/1/Amelio_2-14peddrdr01sf4.pdf"/> </rdf:Description> </rdf:RDF>

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