TAp73 transcriptionally represses BNIP3 expression |
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| Authors: | Varvara Petrova Mara Mancini Massimiliano Agostini Richard A Knight Margherita Annicchiarico-Petruzzelli Nikolai A Barlev Gerry Melino Ivano Amelio |
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| Affiliation: | 1.Medical Research Council; Toxicology Unit; Leicester University; Leicester, UK;2.Molecular Pharmacology Laboratory; Saint-Petersburg Institute of Technology; Saint-Petersburg, Russia;3.Department of Experimental Medicine and Surgery; University of Rome “Tor Vergata”; Rome, Italy;4.Biochemistry Laboratory IDI-IRCC; Rome, Italy;5.Gene Expression Laboratory; Institute of Cytology; Saint-Petersburg, Russia |
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| Abstract: | TAp73 is a tumor suppressor transcriptional factor, belonging to p53 family. Alteration of TAp73 in tumors might lead to reduced DNA damage response, cell cycle arrest and apoptosis. Carcinogen-induced TAp73−/− tumors display also increased angiogenesis, associated to hyperactivition of hypoxia inducible factor signaling. Here, we show that TAp73 suppresses BNIP3 expression, directly binding its gene promoter. BNIP3 is a hypoxia responsive protein, involved in a variety of cellular processes, such as autophagy, mitophagy, apoptosis and necrotic-like cell death. Therefore, through different cellular process altered expression of BNIP3 may differently contribute to cancer development and progression. We found a significant upregulation of BNIP3 in human lung cancer datasets, and we identified a direct association between BNIP3 expression and survival rate of lung cancer patients. Our data therefore provide a novel transcriptional target of TAp73, associated to its antagonistic role on HIF signaling in cancer, which might play a role in tumor suppression. |
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| Keywords: | autophagy HIF lung cancer p73 p53 |
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