Development of Bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer

作者：Cato Laura; Neeb Antje; Sharp Adam; Buzon Victor; Ficarro Scott B; Yang Linxiao; Muhle Goll Claudia; Kuznik Nane C; Riisnaes Ruth; Rodrigues Daniel Nava; Armant Olivier; Gourain Victor; Adelmant Guillaume; Ntim Emmanuel A; Westerling Thomas; Dolling David; Rescigno Pasquale; Figueiredo Ines; Fauser Friedrich; Wu Jennifer; Rottenberg Jaice T; Shatkina Liubov; Ester Claudia; Luy Burkhard; Puchta Holger; Troppmair Jakob; Jung Nicole; Braese Stefan; Straehle Uwe

来源：eLife, 2017, 6: e27159.

DOI：10.7554/eLife.27159

Targeting 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.

• 出版日期2017-8-10