title: TAp73 transcriptionally represses BNIP3 expression.
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.
authors.affiliation: a Medical Research Council; Toxicology Unit; Leicester University ; Leicester , UK.
authors.forename: Varvara
authors.initials: V
authors.lastname: Petrova
authors.forename: Mara
authors.initials: M
authors.lastname: Mancini
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Agostini
authors.forename: Richard A
authors.initials: RA
authors.lastname: Knight
authors.forename: Margherita
authors.initials: M
authors.lastname: Annicchiarico-Petruzzelli
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Barlev
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.forename: Ivano
authors.initials: I
authors.lastname: Amelio
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis*; D009389:Neovascularization, Pathologic / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000235:genetics*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C090121:BNIP3 protein, human; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
keywords: HIF; autophagy; lung cancer; p53; p73