The T850D Phosphomimetic Mutation in the Androgen Receptor Ligand Binding Domain Enhances Recruitment at Activation Function 2.

ABSTRACT: Several key functions of the androgen receptor (AR) such as hormone recognition and co-regulator recruitment converge in the ligand binding domain (LBD). Loss- or gain-of-function of the AR contributes to pathologies such as the androgen insensitivity syndrome and prostate cancer. Here, we describe a gain-of-function mutation of the surface-exposed threonine at position 850, located at the amino-terminus of Helix 10 (H10) in the AR LBD. Since T850 phosphorylation was reported to affect AR function, we created the phosphomimetic mutation T850D. The AR T850D variant has a 1.5- to 2-fold increased transcriptional activity with no effect on ligand affinity. In the androgen responsive LNCaP cell line grown in medium with low androgen levels, we observed a growth advantage for cells in which the

SUBMITTER: Helsen C 

PROVIDER: S-EPMC8836279 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature