Cato, LauraNeeb, AntjeSharp, AdamBuzón, VictorFicarro, Scott BYang, LinxiaoMuhle-Goll, ClaudiaKuznik, Nane CRiisnaes, RuthNava Rodrigues, DanielArmant, OlivierGourain, VictorAdelmant, GuillaumeNtim, Emmanuel AWesterling, ThomasDolling, DavidRescigno, PasqualeFigueiredo, InesFauser, FriedrichWu, JenniferRottenberg, Jaice TShatkina, LiubovEster, ClaudiaLuy, BurkhardPuchta, HolgerTroppmair, JakobJung, NicoleBräse, StefanSträhle, UweMarto, Jarrod ANienhaus, Gerd UlrichAl-Lazikani, BissanSalvatella, Xavierde Bono, Johann SCato, Andrew CBBrown, Myles2017-12-062017Cato, L., A. Neeb, A. Sharp, V. Buzón, S. B. Ficarro, L. Yang, C. Muhle-Goll, et al. 2017. “Development of Bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer.” eLife 6 (1): e27159. doi:10.7554/eLife.27159. http://dx.doi.org/10.7554/eLife.27159.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492209Targeting the activation function-1 (AF-1) domain located in the N-terminus of the androgen receptor (AR) is an attractive therapeutic alternative to the current approaches to inhibit AR action in prostate cancer (PCa). Here we show that the AR AF-1 is bound by the cochaperone Bag-1L. Mutations in the AR interaction domain or loss of Bag-1L abrogate AR signaling and reduce PCa growth. Clinically, Bag-1L protein levels increase with progression to castration-resistant PCa (CRPC) and high levels of Bag-1L in primary PCa associate with a reduced clinical benefit from abiraterone when these tumors progress. Intriguingly, residues in Bag-1L important for its interaction with the AR AF-1 are within a potentially druggable pocket, implicating Bag-1L as a potential therapeutic target in PCa.en-USprostate cancerandrogen receptorBag-1Ltranscription factorsHumanJournal Article2017-12-0610.7554/eLife.27159