Mechanisms that regulate androgen receptor transcriptional activity
TLDR DHT enhances androgen receptor activity more than testosterone, and MAGE-11 influences this activity through specific interactions.
The study investigated the differential effects of testosterone (T) and dihydrotestosterone (DHT) on androgen receptor (AR) activity, revealing that DHT's slower dissociation from AR and stronger stabilization of the AR ligand binding domain (LBD) enhances AR transactivation. The research also explored how the coregulator melanoma antigen gene protein-A11 (MAGE-11) modulates AR activity independently of the AF2 site. MAGE-11, through its F-box, interacts with the AR FXXLF motif, and its phosphorylation by MAP kinase affects this interaction. MAGE-11 forms a complex with coactivators TIF2 and p300, influencing AR transcriptional activity both in the presence and absence of ligands, highlighting a novel role for F-box proteins in AR regulation.