Chaperones for proper androgen action - a plethora of assistance to androgen receptor function

Abstract The androgen receptor (AR) plays a major role for normal prostate growth and also promotes the development and progression of prostate cancer (PCa). PCa, an important age-related disease, is one of the most commonly diagnosed cancers and the second leading cause of cancer mortality for men in Western countries. AR function and activity are regulated by molecular chaperones. The AR belongs to the steroid hormone receptor (SHR) family and can be activated by androgens such as dihydrotestosterone. SHRs are ligand-dependent transcription factors that are predominantly localized in the cytoplasm in the absence of their appropriate ligand. Upon hormone binding, translocation to the nucleus occurs as shown for glucocorticoid receptors, mineralocorticoid receptors, or the AR, while others, such as estrogen and progesterone receptors, are mainly nuclear. Importantly, the newly synthesized and unliganded receptors bind stepwise with chaperones then being associated in a dynamic chaperone heterocomplex, including heat shock proteins. It emerges that chaperones are very important, not only in the proper folding of the AR but they are also involved in receptor stability, intracellular localization and androgen-controlled transcription. Accordingly, chaperones may be interesting future targets for PCa treatment. In this review we will summarize the involvement of chaperones controlling AR activity.