| First Author | Amelio I | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 1 | Pages | 226-31 |
| PubMed ID | 25535359 | Mgi Jnum | J:218243 |
| Mgi Id | MGI:5617073 | Doi | 10.1073/pnas.1410609111 |
| Citation | Amelio I, et al. (2015) TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1alpha degradation. Proc Natl Acad Sci U S A 112(1):226-31 |
| abstractText | 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 (alpha) of HIF-1 and recruits mouse double minute 2 homolog into the protein complex, thus promoting HIF-1alpha 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. |
