Transcriptional repression of the tumor suppressor DRO1 by AIB1

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.

► Tumor suppressor DRO1 (CCDC80) is transcriptionally repressed by AIB1.
► AIB1 repression domain localizes in the distal promoter of DRO1.
► Ectopic expression of DRO1 promotes BCLAF1 expression.
► DRO1 shuttles to the endoplasmic reticulum upon apoptotic stimulation.