Systematic structure-function analysis of androgen receptor Leu701 mutants explains the properties of the prostate cancer mutant L701H.

ABSTRACT: One mechanism of prostate tumors for escape from androgen ablation therapies is mutation of the androgen receptor (AR). We investigated the unique properties of the AR L701H mutant, which is strongly stimulated by cortisol, by a systematic structure-function analysis. Most amino acid substitutions at position 701 did not affect AR activation by 5alpha-dihydrotestosterone. Further analysis of the AR Leu(701) variants showed that AR L701M and AR L701Q, like AR L701H, had changed ligand responsiveness. AR L701M was strongly activated by progesterone but not by cortisol, whereas the opposite was observed for AR L701Q and AR L701H. Next, we analyzed a panel of structurally related steroids to study which of the OH groups at positions 11beta, 17alpha, and 21, which discriminate cortisol from pro

SUBMITTER: van de Wijngaart DJ 

PROVIDER: S-EPMC2836112 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature