A complex with poly(A)-binding protein and EWS facilitates the transcriptional function of oncogenic ETS...

The ETS transcription factor ERG is aberrantly expressed in approximately 50% of prostate tumors due to chromosomal rearrangements such as TMPRSS2/ERG. The ability of ERG to drive oncogenesis in prostate epithelial cells requires interaction with distinct coactivators, such as the RNA-binding protein EWS. Here, we find that ERG has both direct and indirect interactions with EWS, and the indirect interaction is mediated by the poly-A RNA-binding protein PABPC1. PABPC1 directly bound both ERG and EWS. ERG expression in prostate cells promoted PABPC1 localization to the nucleus and recruited PABPC1 to ERG/EWS-binding sites in the genome. Knockdown of PABPC1 in prostate cells abrogated ERG-mediated phenotypes and decreased the ability of ERG to activate transcription. These findings define a complex including ERG and the RNA-binding proteins EWS and PABPC1 that represents a potential therapeutic target for ERG-positive prostate cancer and identify a novel nuclear role for PABPC1.