TAp73 transcriptionally represses BNIP3 expression

• Published in: Cell cycle (Georgetown, Tex.) Vol. 14; no. 15; pp. 2484 - 2493
• Main Authors: Petrova, Varvara, Mancini, Mara, Agostini, Massimiliano, Knight, Richard A, Annicchiarico-Petruzzelli, Margherita, Barlev, Nikolai A, Melino, Gerry, Amelio, Ivano
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 03.08.2015
• Subjects: Apoptosis - genetics; Binding Sites - genetics; Cell Line; DNA-Binding Proteins - genetics; Genes, Tumor Suppressor; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Membrane Proteins - biosynthesis; Neovascularization, Pathologic - genetics; Nuclear Proteins - genetics; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins - biosynthesis; Transcription, Genetic - genetics; Tumor Protein p73; Tumor Suppressor Proteins - genetics; lung cancer; autophagy; HIF; p73; p53
• ISSN: 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2015.1044178

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.