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

TitleTAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation
Authors
KeywordsVEGF
P53 family
P73
Tumor progression
Tumor vascularization
Issue Date2015
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2015, v. 112, n. 1, p. 226-231 How to Cite?
AbstractTumor 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.
Persistent Identifierhttp://hdl.handle.net/10722/292861
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorAmelio, Ivano-
dc.contributor.authorInoue, Satoshi-
dc.contributor.authorMarkert, Elke K.-
dc.contributor.authorLevine, Arnold J.-
dc.contributor.authorKnight, Richard A.-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorMelino, Gerry-
dc.date.accessioned2020-11-17T14:57:22Z-
dc.date.available2020-11-17T14:57:22Z-
dc.date.issued2015-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2015, v. 112, n. 1, p. 226-231-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/292861-
dc.description.abstractTumor 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.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectVEGF-
dc.subjectP53 family-
dc.subjectP73-
dc.subjectTumor progression-
dc.subjectTumor vascularization-
dc.titleTAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1410609111-
dc.identifier.pmid25535359-
dc.identifier.pmcidPMC4291637-
dc.identifier.scopuseid_2-s2.0-84920492117-
dc.identifier.volume112-
dc.identifier.issue1-
dc.identifier.spage226-
dc.identifier.epage231-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000347447100057-
dc.identifier.issnl0027-8424-

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