Phase separation as a potential mechanism to control the transcriptional activity of the androgen receptor.

ROGGERO, CARLOS M.; ESSER, V.E.; RIZO, JOSEP

DALLAS, TEXAS

Simposio; Prostate Cancer Symposium: Global management of prostate cancer. UT Sothwestern Medical Center, Dallas TX.; 2018

Prostate cancer is the most common form of cancer in men, currently leading to more than 30.000 deaths per year in US. Signaling through the androgen receptor (AR) is critical for survival and proliferation of prostate cancer cells. Consequently, standard therapies against prostate cancer involve androgen reduction through chemical or surgical castration. However, patients invariably develop the more aggressive castration-resistant prostate cancer (CRPC), for which there is no satisfactory treatment. The mechanisms that contribute to development of CRPC remain to be stablished, but it seems clear that AR remains active; even a small increase in AR expression can result in tumor resistance to castration. Hence, there is an urgent need to find alternative therapies that are not solely based on hormone deprivation. Several members of the JMJD family have been implicated in AR regulation and prostate cancer. We found that low-complexity sequences appear to be critical for AR-JMJD2 interactions and that the length of a polyQ sequence at the AR NTD is inversely correlated with propensity to PCA. We found that AR NTD mediates phase separation and the polyQ length influences this property, and this property may be involved in the control of AR activity.