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. © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.This work was supported by grants SAF2009-08334 from Spanish Ministry of Science and Innovation; EVES 047/2008 from Conselleria de Sanitat and ACOMP/2009/001 from Consellería d’Educació i Ciencia, both from Generalitat Valenciana. A. Pla was supported by a pre-doctoral fellowship from the Conselleria d’Educació from Generalitat Valenciana. J De Las Rivas thanks the support provided by MICINN-ISCiii reference PS09/00843.Peer Reviewe