title: Transcriptional repression of the tumor suppressor DRO1 by AIB1.
abstract: Using transcriptomic gene expression profiling we found tumor suppressor DRO1 being repressed in AIB1 transgenic mice. In agreement, AIB1 represses DRO1 promoter and its expression levels inversely correlate with DRO1 in several cancer cell lines and in ectopic and silencing assays. Estrogen modulators treatment showed a regulation in an estrogen receptor-dependent fashion. Importantly, DRO1 overexpression resulted in BCLAF1 upregulation, a compelling concept given that BCLAF1 is a death-promoting transcriptional repressor. Additionally, DRO1 shuttles from Golgi to the endoplasmic reticulum upon apoptotic stimuli, where it is predicted to facilitate the apoptosis cascade. Finally, DRO1 repression is an important factor for AIB1-mediated inhibition of apoptosis. Collectively, our results reveal DRO1 as an AIB1-targeted tumor suppressor, providing a novel mechanism for AIB1-dependent inhibition of apoptosis.
authors.affiliation: Laboratory of Cellular and Molecular Biology, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Ferragud
authors.forename: Alvaro
authors.initials: A
authors.lastname: Avivar-Valderas
authors.forename: Antoni
authors.initials: A
authors.lastname: Pla
authors.forename: Javier
authors.initials: J
authors.lastname: De Las Rivas
authors.forename: Jaime
authors.initials: J
authors.lastname: Font de Mora
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D016326:Extracellular Matrix Proteins; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C492631:CCDC80 protein, human; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D025521:Tumor Suppressor Proteins; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3